Program

Time	Program Outline	Room
1400-1630	IATDMCT Council Meeting	KC 310

Time	Program Outline	Room
0800-1000	Meeting with Scientific Committee and Regional Section Chairs/Co-Chairs	KC 305
1000-1500	Pre-Congress Symposium: New Frontiers in Clinical Toxicology	Max Bell
1600-1730	Opening Ceremony Keynote Speaker	KC 101/103/105
1730-1930	Welcome Reception in the Exhibit Hall	KC 201/203/205
1930	Free Evening

 
1000-1500 Pre-Congress Symposium: New Frontiers in Clinical Toxicology
 

1000-1005	Welcome
1005-1050	Leveraging a Wastewater-based Surveillance Network for SARS-CoV-2 to Understand Population Patterns of Substance Use Michael D. Parkins, University of Calgary, Canada   At the end of this session participants will be able to: List the scope of targets that can be monitored through Wastewater-based surveillance. Explain the role of WBS at a different range of scales across populations. Discuss additional metadata to include with WBS to provide granular surveillance of substance use, and toxicities across populations. Summarize the benefits and limitations of wastewater-based surveillance. The presentation will review the efforts and outputs of a transdisciplinary team from the UCalgary to develop and implement a WBS program for substances of abuse across a range of scales.
1050-1105	Refreshment Break
1105-1150	Drug Checking: Drug Testing at the Intersection of Clinical Toxicology and Harm Reduction Cristiana Stefan, The Centre for Addiction and Mental Health, Canada   At the end of this session participants will be able to: Explain the concept of drug checking in relation to drug analytical testing and drug harm reduction principles. Discuss the potential of the clinical toxicology laboratories to engage in the testing of unregulated (street) drug supplies to support harm reduction strategies. Recognize the impact of legislative requirements for controlled substances when implementing drug checking activities in a laboratory setting. Explain the main drug findings and trends from the Toronto’s Drug Checking Service Project and their overall influence on public health response and clinical practice. In the past decades, drug checking has emerged as an essential public health response to reduce the harms associated with the exposure to Novel Psychoactive Substances (NPS), notably synthetic opioids. At the core of drug checking, a term introduced to reduce the stigma experienced by the People Who Use Drugs (PWUD), is the actual testing of the unregulated (street) drug supplies sold to PWUD. The clinical toxicology laboratories are conventionally involved with drug testing in biological specimens for patient care, using automated, commercially available tests (mainly immunoassays) and/or laboratory-developed tests. Their potential to support harm reduction efforts through direct testing of the street drugs sold to PWUD has only been explored and recognized in recent years. This presentation is based on the speaker’s direct involvement with Toronto’s Drug Checking Service, launched in October 2019 as part of an interdisciplinary community, hospital, and laboratory collaboration sponsored primarily by Health Canada to address Toronto’s opioid crisis. The speaker will discuss the legislative requirements for controlled substances to integrate this project in the overall operation of the clinical laboratory, and the in-house developed analytical protocols and algorithms for NPS detection based on liquid chromatography coupled to Orbitrap high-resolution mass spectrometry principles. Drug findings and trends, notably of fentanyl analogues, benzimidazole (nitazene) opioids, designer benzodiazepines and other harmful CNS depressants classes will be presented; in addition to their overall impact on the public health response to the opioid crisis.
1150-1230	Lunch
1230-1315	Use of Artificial Intelligence (AI) to Predict and Identify Novel Illicit Drugs David Wishart, University of Alberta, Canada   At the end of this session participants will be able to: Describe at a general level the concepts behind chemical language models for generating compounds. Discuss at a general level how AI can be used to predict mass spectra of chemicals. Summarize how AI can assist with the rapid identification of novel or illicit drugs. The identification of drugs, especially novel or previously unknown street drugs, can take weeks of difficult laboratory work. This is often far too long to help either with the care of patients who have been poisoned or in managing a drug-poisoning outbreak. In this presentation the speaker will describe how artificial intelligence (AI) can be used to not only predict the appearance of new, illegal drugs, but also predict their structures and their characteristic mass spectra. This information is needed to identify illegal drug compounds from blood, urine or recovered drug paraphernalia. This novel approach to illegal drug (and other compound) identification opens the door to being able to rapidly detect new pyschoactive substances or other kinds of harmful (illegal or legal) drugs and toxins that may be inadvertently, or deliberately consumed by individuals.
1315-1330	Refreshment Break
1330-1415	Public Health and Safety Impacts of Cannabis Legalization in Canada Shea Wood, Canadian Centre on Substance Use and Addiction, Canada   At the end of this session participants will be able to: Describe the key components and objectives of the Cannabis Act in Canada. Identify the impacts of cannabis legalization and various regulations on public health and safety, including observed benefits and potential areas of concern. Summarize remaining knowledge gaps and outline future priorities in cannabis-related policy development, research, prevention strategies, and public education efforts. This session will provide an overview of the Cannabis Act and Canada’s progress towards its public health and safety objectives. It will address the evolving legal cannabis market and the impacts of legalization and regulations on cannabis use among people in Canada. This will be followed by a discussion on the observed benefits of cannabis legalization in Canada and some areas of concern. Finally, future priorities in policy development, research, prevention, and public education will be addressed.
1415-1500	Semi-synthetic and Hemp-derived Cannabinoids: An Activity Perspective Christophe Stove, Ghent University, Belgium   At the end of this session participants will be able to: Discuss the problem of semi-synthetic and hemp-derived cannabinoids. Explain how activity-based assessment may allow to prioritize substances of higher concern. Summarize remaining knowledge gaps and outline future priorities. This lecture will provide an overview of how semi-synthetic and hemp-derived cannabinoids evolved, and why they may pose a legislative, analytical and potential health issue. It will explain how pharmacological assessment of the cannabinoid receptor (1 (CB1) activation potential may allow prioritization of those compounds that pose the highest risk, and will describe how end products containing these substances can be characterized based on composition and CB1 activity.

Time	Program Outline			Room
0715-0815	Breakfast Roundtables R1601: Gut microbiome in individual variability to drug response R1602: The controversy on statin health outcomes: a gap between fundamental science and clinical evidence R1603: What is the molecularly imprinted? How will molecularly imprinted sensors change the world of TDM? R1604: Challenges of High-Resolution Mass Spectrometry for Drug Testing R1605: TDM of biologics in oncology: is there room for personalized dosing for anti-body drug conjugates R1606: Research integrity in TDM and CT			KC 305
0830-0930	Plenary Presentation: Promise of Psychedelics			KC 101/103/105
0930-1000	Refreshment Break and Exhibit Viewing			KC 201/203/205
1000-1130	Symposium: Alternative Sampling Strategies	Symposium: Anti-Infective Drugs	Symposium: TDM of Biologics	Max Bell Bldg
1130-1300	Lunch and Exhibit Viewing			KC 201/203/205
	Industry Workshop: Advances in High Throughput Paper-Spray Mass Spectrometry (PS-MS) for TDM, Harm Reduction Drug Testing and Clinical Diagnostic Application			KC 305
1300-1430	Oral Presentations			Max Bell Bldg
1430-1500	Refreshment Break and Exhibit Viewing			KC 201/203/205
1500-1600	Poster Viewing
1600-1730	Symposium: Pharmacogenetics	Symposium: TDM in Oncology	Symposium: Young Scientists Symposium	Max Bell Bldg
1730-1900	IATDMCT Annual General Meeting and Award Presentations Victor Armstrong Young Investigator Award Patsalos Award			KC 101/103/105
1900-2030	Wine & Cheese Reception and Exhibit Viewing			KC 201/203/205

 
0715-0815 Breakfast Roundtables
 
R1601: Gut microbiome in individual variability to drug response
Roland Lawson, University of Limoges, France
 
At the end of this session participants will be able to:

• Explain the bidirectional interaction between drugs and the gut microbiome.
• Discuss the impact of the gut microbiome in response to immunosuppressants.
• Discuss potential strategies in the road to precision medicine by targeting the gut microbiome.

The gut microbiome has emerged as a potent drug metabolism ‘organ’, capable of the same type of reactions as the liver or other metabolic organs. The gut microbiome can activate or inactivate drugs, induce toxicity or inefficacy in the host, and influence the pharmacokinetic profile of drugs. The translation of microbiome research into impactful clinical applications for patients requires a robust and structured approach that could help build mechanistic and predictive pharmacokinetic models and develop reliable efficacy and safety models. This session will discuss the contribution of gut microbiome studies to improve TDM of immunosuppressive drugs and explore the gut microbiome as a new frontier in TDM and toxicology.
 
R1602: The controversy on statin health outcomes: a gap between fundamental science and clinical evidence
Hundie Tesfaye, Charles University and Motol University Hospital, Czech Republic
 
At the end of this session participants will be able to:

• Underline that there is a great deal of research yet to be done to improve the state of the art.
• Avoid generally advocating the baseless theory “the lowest is the best” in the case of cholesterol.
• Reconsider where to block the process of atherosclerosis than concentrating too much on blood cholesterol levels at large.
• Rethink about life quality and statins case relationship beyond lowering cholesterol.

This session will discuss the current controversy on statin health outcomes. A generally declared belief is that cholesterol concentrations should be kept low to reduce the risk of cardiovascular diseases. However, studies of the relation between serum cholesterol and all-cause mortality in people on statins treatment have shown contrasting results. Some studies failed to show benefits of too low cholesterol casting doubt on the scientific justification for lowering cholesterol. More importantly, patients on statins present well-defined adverse effects such as myotoxicity including rhabdomyolysis progressing to renal failure.
 
R1603: What is the molecularly imprinted? How will molecularly imprinted sensors change the world of TDM?
Yasuo Yoshimi, Shibaura Institute of Technology, Japan
 
At the end of this session participants will be able to:

• Explain that the MIP sensor is a simple and fast drug detection sensor.
• Discuss how this sensor will change the field of TDM.
• Discuss with the developer about what improvements should be made to the sensor for effective use in the field of TDM.

The research team of the chair is developing disposable sensors that can measure serum concentrations of various high-risk drugs such as vancomycin in a few tens of seconds, which is expected to significantly reduce the time, effort, and cost of analyzing blood levels required for TDM. The chair will discuss with pharmacists and physicians how this sensor will change the flow of TDM and what specifications are needed for the sensor to be widely used. The discussion will include:
– Explanation of the principle of operation of the sensor.
– Demonstration of the sensor prototype.
– Discussion on how sensors can be used in the TDM field and what can be improved for this purpose.
 
R1604: Challenges of High-Resolution Mass Spectrometry for Drug Testing
Hans H. Maurer, Saarland University, Germany
 
At the end of this session participants will be able to:

• Explain the possibilities and limitations of HRMS for drug testing.
• List the challenges should be considered when applying HRMS.
• Discuss how can these challenges be overcome.

Today, high-resolution mass spectrometry (HRMS) coupled to liquid chromatography (LC), gas chromatography (GC), capillary electrophoresis (CE), or paperspray (PS) is increasingly applied for drug testing etc. It provides universality, high selectivity, specificity, sensitivity, and reproducibility. Nevertheless, some challenges have to be considered such as need of experienced staff, huge amount of data to be handled, integration and automation of several data analysis software packages, regularly updated reference libraries working on all available MS platforms, differentiation of isomers, and finally, harmonization of acceptance criteria for identification.
During the roundtable, these challenges, presented by the chair and contributed by the participants, will be discussed.
References
Maurer HH, Drug Test Anal. 2020, 172.
Maurer HH, Anal Bioanal Chem 2021, 2303.
Strathmann FG et al., Clin Chem 2020, 868.
Wille SM et al., Curr Pharm Des 2022, 1230.
 
R1605: TDM of biologics in oncology: is there room for personalized dosing for anti-body drug conjugates
Dirk Jan Moes, Leiden University Medical Center, Netherlands
 
At the end of this session participants will be able to:

• Explain the mechanism of action of ADCs and variability in exposure of ADCs.
• List the bioanalytical challenges of ADCs.
• Discuss potential strategies to personalize the dose in order to reduce toxicity.

Antibody drug conjugates (ADCs) represent a ground-breaking new class of anticancer drugs. ADCs combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs. This innovative approach leverages the targeting capabilities of antibodies to deliver cytotoxic payloads selectively to cancer cells and thereby minimizing systemic toxicity and maximizing therapeutic efficacy. Over the past few decades, ADCs have emerged as a promising class of anticancer drugs, with many under research and increasing number of ADCs receiving regulatory approval for the treatment of various cancers. Despite the hope of a “magic bullet”, often toxicity limits the dose before maximum efficacy is reached. A substantial fraction of patients require dose modifications or treatment discontinuation due to intolerable ADC associated toxicity. Toxicity is rarely driven by target expression in healthy tissue is a usually independent of cancer type. Furthermore, high body weight has been associated with increased risk of peripheral neuropathy. In principle both the payload as well as the antibody can be measured, however which is most relevant. Both LC-MS/MS as well as immunoassays are suitable to measure the antibody. In this round table session the opportunities and ideas to explore and investigate the added value of personalized dosing of ADC’s well be discussed in an informal manner.
 
R1606: Research integrity in TDM and CT
Teun van Gelder, Leiden University Medical Center, Netherlands
 
At the end of this session participants will be able to:

• Discuss the motives of fraudsters, that can vary from personal greed, financial necessity, ideological beliefs, the thrill of defying the system, and others.
• Explain how lack of integrity can cause direct damage (for example to patients) and can affect public trust in science and trust between scientists.
• Provide recommendations for institutions on how they can create a working environment that promotes and safeguards good research practices.

Integrity is essential for scientific research. The normativity is partly methodological and partly ethical in nature, and can be expressed in terms of a number of guiding principles: honesty, scrupulousness, transparency, independence and responsibility. Researchers who are not guided by these principles risk harming both the quality and the trustworthiness of research. This can take the form of direct damage, for example to the environment or to patients, and can undermine public trust in scientific research as well as mutual trust between individual researchers. In the workshop we will discuss some examples of lack of integrity, and on how to act if you suspect one of your colleagues is committing fraud (such as fabrication of data, falsification of data, plagiarism, …). And of course you are welcome to explain to us how you have committed fraud yourself 😊!
 
 
 
0830-0930 Plenary Presentation: Promise of Psychedelics
Peter Silverstone, University of Alberta, Canada
 
At the end of this session participants will be able to:

• List potential therapeutic roles for psychedelics.
• Discuss potential mechanism of actions for psychedelics.
• Discuss potential risks and toxicology issues for psychedelics.

This session will provide a detailed overview of the potential use of psychedelics as medications both in psychiatry and in other areas, and will provide current neuroscience updates and pathophysiology which have the potential to make these drugs of huge interest in multiple clinical areas.
 
 
 
1000-1130 Symposium: Microsampling
Presented by the Alternative Sampling Strategies Committee
Co-Chairs:
Christophe Stove, Ghent University, Belgium
Suzanne Parker, The University of Queensland, Australia
 
Presentations:
 
To convert or not to convert? Considerations and recommendations to convert capillary blood microsampling concentrations to plasma concentrations
Laura Boffel, Ghent University, Belgium
 
At the end of this session participants will be able to:

• Explain the differences between capillary blood concentrations and plasma concentrations.
• Make an informed decision about whether it is appropriate or desired to convert capillary blood microsampling concentrations to plasma concentrations.
• Discuss how to translate or convert capillary blood microsampling concentrations to plasma concentrations.

Capillary blood microsampling, a minimally invasive technique, enables the collection of small blood volumes, making it particularly suitable for e.g., remote sampling and vulnerable populations. However, capillary blood differs from venous blood in composition, which can affect the concentrations of the envisaged analyte(s). Moreover, analytes vary in their distribution between the blood cell and plasma fractions, leading to potential differences in levels between plasma and capillary blood. Since plasma is often the standard matrix for routine analyses, this discrepancy can compromise the clinician’s interpretation of capillary blood microsampling concentrations. Hence, to ensure comparability with (i) results obtained via standard plasma assays and (ii) reference ranges established in plasma, accurate conversion to plasma concentrations might be needed, which might moreover improve the reliability and validity of the microsampling-based assays. Despite the high relevance of this topic, general considerations about whether conversion is appropriate or desired and recommendations to translate capillary blood microsampling concentrations to plasma concentrations are currently lacking. Therefore, our aim is to discuss the ‘what, when and how’ of converting capillary to plasma concentrations and also provide generally applicable considerations and recommendations in this context.
 
Selected Abstract: ADVANCED trial: A clinical trial on dried blood spot samples and venepuncture plasma samples for monitoring vancomycin and creatinine simultaneously in trauma and orthopedic adult patients
Moska Hassanzai, Erasmus MC, Netherlands
 
Selected Abstract: Clinical validation of a volumetric absorptive microsampling LC-MS/MS method for quantification of MPA and MPAG in kidney transplant recipients
Ole Martin Drevland, University of Oslo, Norway
 
Continuous real-time monitoring of drugs to deliver personalised dosing
Sophie Stocker, The University of Sydney, Australia
 
At the end of this session participants will be able to:

• Explain how biosensors work.
• Identify therapeutic areas where biosensors have clinical utility.
• Assess what additional research is required to support implementation of biosensors into practice.

By ensuring optimal dosing, therapeutic drug monitoring (TDM) improves outcomes in critically ill patients by maximizing effectiveness while minimizing toxicity. Current methods for measuring plasma drug concentrations, however, can be challenging, time-consuming, and slow to return an answer, limiting the extent to which TDM is used to optimize drug exposure. A potentially promising solution to this dilemma is provided by biosensors, molecular sensing devices that employ biorecognition elements to recognize and quantify their target molecules rapidly and in a single step. This presentation reviews the current state of the art for biosensors regarding their application to TDM, both as ex vivo point-of-care devices supporting single timepoint measurements and in vivo devices supporting continuous real-time monitoring in situ in the body. This presentation also discusses the clinical development of biosensors for TDM, including regulatory challenges and the need for standardized performance evaluation. Through precise and real-time monitoring of drugs, the application of biosensors in TDM holds great promise for enhancing the optimization of drug exposure particularly in critically ill patients, offering the potential for improved outcomes.
 
 
 
1000-1130 Symposium: The mysteries of target site concentrations of antibiotics in hard to reach infections: an evolving application of TDM?
Presented by the Anti-Infective Drugs Committee
Co-Chairs:
Dario Cattaneo, L. Sacco University Hospital, Italy
Birgit Koch, Erasmus MC, Netherlands
 
Presentations:
 
TDM of long-acting antibiotics for long-term use
Milo Gatti, University of Bologna, Italy
 
At the end of this session participants will be able to:

• Identify the best PK/PD target for dalbavancin in the management of Staphylococcal infections.
• Assess the relationship between optimal dalbavancin PK/PD target and clinical efficacy in long-term infection.
• Adopt a TDM-guided strategy for optimizing dalbavancin exposure in long-term infections.

The presentation will focus on the PK/PD optimization of long-acting agents (i.e., dalbavancin and oritavancin) according to a TDM-guided strategy for the management of long-term infections.
 
Stability issues and potential role of TDM for outpatient parenteral antibiotic therapies
Birgit Koch, Erasmus MC, Netherlands
 
At the end of this session participants will be able to:

• Discuss of stability if antibiotics in OPAT.
• Explain the added value of TDM in OPAT.
• Outline the possible role of alternative sampling in OPAT.

Outpatient Parenteral Antimicrobial Therapy (OPAT) is a critical approach in managing infections that require intravenous antibiotics outside the hospital setting. It allows patients to receive effective treatment while minimizing hospital stays, reducing healthcare costs, and improving patient quality of life. Understanding the stability of antibiotics is essential in OPAT to ensure the efficacy of the medication throughout its administration, particularly when storage conditions vary outside a controlled hospital environment. Therapeutic Drug Monitoring (TDM) plays a vital role in OPAT for antibiotics with narrow therapeutic indices, where maintaining optimal drug levels is crucial to avoid toxicity or treatment failure. TDM ensures individualized dosing, adjusting for factors like renal function or drug interactions, which is particularly important in a home setting where close monitoring is challenging.
Alternative sampling methods, such as dried blood spots or microsampling, offer a practical solution in OPAT for collecting samples with minimal disruption to the patient. These methods enable regular monitoring without the need for frequent hospital visits, making TDM more feasible and effective in outpatient settings. By integrating TDM and alternative sampling into OPAT, healthcare providers can enhance the safety and effectiveness of antibiotic therapy, leading to better patient outcomes.
This talk will give an update on stability, alternative sampling options and clinical studies related to OPAT and TDM of antibiotics.
 
Deciphering and quantifying the penetration of antibiotics in tissues
Iris K. Minichmayr, Medical University of Vienna, Austria
 
At the end of this session participants will be able to:

• Outline key factors influencing the penetration of antibiotics into various tissues.
• Explain approaches for quantifying drug concentrations in different biological matrices.
• Discuss challenges and opportunities in performing TDM based on target-site concentrations.

This session will address the challenges and advancements in understanding antibiotic penetration into peripheral tissues. It will explore methodologies for quantifying tissue distribution, particularly in the context of hard-to-treat infections. Further emphasis will be placed on the evolving role of therapeutic drug monitoring in optimizing target-site concentrations to improve clinical outcomes in challenging infection scenarios.
 
Using saliva as an alternative matrix to conduct TDM of antibiotics
Anh Thi Nguyen, The University of Sydney, Australia
 
At the end of this session participants will be able to:

• Describe drug excretion into saliva.
• Explain the factors which contribute to variability in excretion of drugs into saliva.
• Relate drug exposure in saliva to that in the blood.
• Identify the optimal protocol for saliva based TDM.

This session will explore the principles and potential applications of saliva-based therapeutic drug monitoring (TDM) for antibiotics. We will begin by exploring the mechanisms of drug excretion into saliva, identifying the key factors that contribute to variability in this process. We will delve into these drug-specific and human-specific factors and discuss how these insights can inform the development of effective saliva-based TDM protocols, ensuring accurate and reliable monitoring. By the end of this session, attendees will have a comprehensive understanding of how saliva can be effectively used in TDM, offering a non-invasive and more accessible alternative for personalised drug dosing.
 
 
 
1000-1130 Symposium: TDM of Biologics
Presented by the TDM of Biologics Committee
Co-Chairs:
Dirk Jan Moes, Leiden University Medical Center, Netherlands
Annick de Vries, Sanquin Diagnostic Services, Netherlands
 
Presentations:
Difficulties in the TDM of Biologics of the highly dosed newer drugs
Femke Hooijberg, Amsterdam UMC, Netherlands
 
At the end of this session participants will be able to:

• Describe the difficulties and challenges of therapeutic drug monitoring (TDM) for biologics.
• Explain potential strategies to overcome these challenges.
• Identify practical considerations in TDM.

This session will explore the various factors that complicate therapeutic drug monitoring (TDM). Key topics include selecting appropriate targets and achieving them through population-based tapering or more individualized, Bayesian-guided tapering. We will also discuss nonlinear clearance mechanisms such as target-mediated drug disposition and the impact of immunogenicity. Additionally, practical considerations will be addressed, such as the choice between dosing strictly by whole weeks versus incorporating single-day dosing, and the need for trough concentration measurements to inform dosing decisions. Through this comprehensive overview, participants will gain a deeper understanding of how to optimize TDM in clinical practice.
 
The association between serum drug concentration and a flare in rheumatoid arthritis patients tapering TNF inhibitors
Zohra Layegh, Erasmus Medical Center and Immunoloy Center Reade, Netherlands
 
At the end of this session participants will be able to:

• Discuss that, while tapering medication in rheumatoid arthritis patients in remission, most flares occur when the mean serum concentration of adalimumab and etanercept drops below 1 mg/L.
• Explain that tapering methotrexate in rheumatoid arthritis patients on long-term adalimumab does not affect the serum concentration of adalimumab, even though there is an increase in anti-drug antibodies against adalimumab.
• Outline how TDM can help identify optimal dosing regimens that balance efficacy and safety, particularly in patients at risk of disease relapse or treatment failure during tapering..

This presentation will focus on measuring serum drug levels in rheumatoid arthritis patients tapering TNFi.
 
Enhancing Pediatric Care: Therapeutic Drug Monitoring of Biologic Agents in Inflammatory Diseases
Ruud Verstegen, The Hospital for Sick Children, Canada
 
At the end of this session participants will be able to:

• Describe how drug metabolism of biological agents differs between children and adults.
• Discuss the complexities of extrapolating target drug concentration recommendations from adults to children.
• Discuss the practical considerations of therapeutic drug monitoring in children.

During this presentation, the audience will gain an understanding of how therapeutic drug monitoring of biologic agents differs between children and adults.
 
Panel Discussion
 
 
 
1300-1430 Oral Presentations
 
 
 
1600-1730 Symposium: Genetic diversity in clinical pharmacogenomics: challenges and opportunities for NGS
Presented by the Pharmacogenetics Committee
Co-Chairs:
Erika Cecchin, National Cancer Institute CRO Aviano, Italy
Jesse Swen, Leiden University Medical Centre, Netherlands
 
Presentations:
Preventing severe fluoropyrimidine induced toxicities in the US – the impact of genetic diversity on testing decisions
Daniel Hertz, University of Michigan College of Pharmacy, USA
 
At the end of this session participants will be able to:

• Describe the evidence supporting the clinical benefit of DPYD testing.
• Recognize that DPYD testing is not standard of care in USA, but is becoming more common.
• Explain the importance of genetic diversity in determining which variants should be included on testing panels.
• Compare the benefits and drawbacks of genotyping and sequencing.

This presentation will describe the evidence supporting the clinical benefits of DPYD testing to prevent severe fluoropyrimidine toxicity. It will then explain the current status of DPYD testing in the USA, including the increase in uptake but barriers to wide-scale adoption. The presenter will then discuss the importance of genetic diversity in the USA and the benefits of using genetic testing techniques that cover the variants carried by diverse patient populations. Finally, the presentation will highlight some potential challenges with clinical implementation of comprehensive genotyping or sequencing testing strategies.
 
Pharmacogenomics in Psychiatry
Daniel Mueller, University of Toronto, Canada
 
At the end of this session participants will be able to:

• Review evidence for clinically actionable gene-drug pairs for psychiatric medications.
• Outline recommendations provided by expert panels and regulatory agencies (e.g., Canada, Europe, USA).
• Address application of pharmacogenetic testing in clinical practice with examples and interaction with the audience.

Prescribers and patients are frequently facing the challenge that treatment standards established at a population level might not be beneficial at the individual level. As a result, lengthy trials are often required before the optimum psychiatric medication treatment, single or in combination, are found. The underlying reasons for this large inter-individual variability treatment outcomes are not fully understood. Important factors that influence drug dose, response and side effects include age, gender, patient compliance, clinical symptoms, co-morbidities, lifestyle, ancestry and genetic factors. In this context, first strategies using pharmacogenetic (PGx) information bear the promise to optimize medication treatment in clinical practice. This presentation will provide state-of-the-art summaries of key concept and strategies of psychiatric PGx: 1) Review the evidence, clinical utility and studies including randomized clinical trials of distinct gene-drug pairs; 2) discuss current expert recommendations (e.g., Clinical Pharmacogenomics Implementation Consortium); 3) how PGx information can be best used in clinical practice, in particular to avoid pseudo-resistance for antidepressants 3) highlight ongoing implementation efforts and 4) provide practical support for psychiatrists, pharmacists and nurses.
 
Variation in nicotine metabolism alters smoking, cessation, and disease risk: Drug monitoring and Pharmacogenomics
Rachel Tyndale, University of Toronto, Canada
 
Selected Abstract: Relationship between gene polymorphisms and the exposure, efficacy, and toxicity of eltrombopag in the treatment of refractory aplastic anemia
Wei Zuo, Peking Union Medical College Hospital, China
 
 
 
1600-1730 Symposium: Innovative ways of Therapeutic Drug Monitoring and Dose optimization in oncology
Presented by the TDM in Oncology Committee
Co-Chairs:
Vikram Gota, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, India
Dirk Jan Moes, Leiden University Medical Centre, Netherlands
 
Presentations:
 
Towards understanding CAR-T cell kinetics and dynamics: Optimization of clinical trials and clinical practice using modelling and simulation
Fenja Klima, Freie Universität Berlin, Germany
 
At the end of this session participants will be able to:

• List the challenges for CAR-T quantification in clinical trials and clinical practice.
• Explain the unique characteristics of CAR-T cells with focus on kinetics.
• Discuss opportunities to optimize CAR-T cell sampling design in clinical trials and clinical practice.
• Discuss challenges and strategies to bridge current knowledge gaps and improve treatment with CAR-T cells.

Chimeric antigen receptor (CAR)-T cell therapy is a novel cellular immunotherapy and has impressively improved treatment outcomes for many cancer patients. However, a substantial percentage of patients initially fails to enter remission or eventually relapses. Therefore, a better understanding of the kinetics and dynamics of CAR-T cells in a patient and of early predictors of response and survival is needed. Pharmacometric modelling and simulation is a powerful tool to integrate clinical data and mechanistic knowledge on CAR-T cell kinetics and dynamics to answer such questions. However, owing to the recent introduction into clinical practice, clinical data on CAR-T cell therapy is rare and highly heterogeneous, often hindering a meaningful evaluation. In my talk I will highlight challenges and knowledge gaps in CAR-T cell therapy. Furthermore, I will discuss strategies and opportunities to optimize and harmonize CAR-T cell sampling in the clinic to bridge these knowledge gaps and to ultimately contribute to a safe and efficacious therapy with CAR-T cell products.
 
Evolutionary therapy for metastatic melanoma: Interim pilot trial results
Alexander Anderson, Moffitt Cancer Center, USA
 
At the end of this session participants will be able to:

• Recognize cancer is a complex evolving system.
• Contrast that control might be a better strategy than cure in metastatic disease.
• Demonstrate that treatments should exploit evolution rather than ignore it.
• Show how quantitative measures of ctDNA can be used in melanoma treatment decision making.

Treatment resistance is one of the greatest challenges in modern cancer therapy. Standard-of-care regimens seek to maximize cell kill in order to achieve a cure. However, if they fail, these approaches free resistant cells from intra-tumoral competition and thereby select for treatment-refractory cancer phenotypes that are often more aggressive upon recurrence. An emerging alternative approach called adaptive therapy aims to tackle this problem by prioritizing tumor control over cure. The idea is to leverage intra-tumoral competition to avoid – or at least slow down – the expansion of therapy-tolerant or resistant tumor subpopulations. Previous results in prostate cancer showed that adaptive application of a single drug using a simple rule of 50% burden reduction to stop treatment for a given patient, could more than double the time to progression and use less than half of the drug. How should adaptive therapy be implemented in different cancers with different drugs? What should we do when multiple drugs are involved? How should we choose treatment switch points?
We present interim results on an adaptive clinical trial (NCT03543969) in metastatic melanoma combining two targeted drugs (Encorafenib, Binimetinib) with a check point inhibitor (Nivolumab). In this pilot study we randomized 10 patients to either a control arm combining all 3 drugs continuously or and adaptive arm. In the adaptive arm we use the immunotherapy as a backbone therapy, given continuously, and adaptively apply the two targeted drugs on a patient-specific basis. Each patient has mutant ctDNA (every 2 weeks), LDH (every 2 weeks), and clinical imaging (every 6 weeks) measurements taken, and these are used to calibrate our mathematical model. The mathematical model, is a simple coupled system of differential equations, incorporates both drug sensitive and resistant populations and importantly allows for a degree of plasticity between these states.
By using our calibrated model for each patient we are able to forecast the future tumor burden, allowing us to make the decision to either maintain or temporarily stop the targeted treatments. Results so far indicate both the adaptive and control arms do a good job of keeping metastatic melanoma under control in these patients, but there is significantly more toxicity in our control arm to the extent where one patient permanently stopped immunotherapy. Mathematical model driven treatment decisions are an important tool for adaptive therapy but are only as effective as their ability to fit and predict patient dynamics, this is particularly relevant issue when patient tumor burdens are low and have limited dynamic change. In this trial we have begun integrating other patient specific information to help understand response dynamics when burdens are static rather than dynamic. Using ctDNA as biomarker of response has raised some key questions: How often should ctDNA be measured? How much change in ctDNA should be considered important? What should we do when ctDNA and LDH levels diverge?
 
Selected Abstract: The relationship between the blood trough concentrations of imatinib and the body compositions in patients with gastrointestinal stromal tumors
Yi Zhou, Chongqing Medical University, China
 
Selected Abstract: Therapeutic drug monitoring and dried blood spot measurements of 5-fluorouracil as 24-hour infusion in patients with gastric cancer treated with perioperative FLOT
Thomas Manten, Catharina Hospital Eindhoven, Netherlands
 
 
 
1600-1730 Symposium: Young Scientists Symposium Presented by the Young Scientists Committee
Co-Chairs:
Anh Thi Nguyen, The University of Sydney, Australia
Lea Wagmann, Saarland University, Germany
 
Presentations:
 
How to investigate the toxicokinetics of new psychoactive substances?
Lea Wagmann, Saarland University, Germany
 
At the end of this session participants will be able to:

• Explain the importance of NPS toxicokinetic studies.
• List different models suitable to study the toxicokinetics of NPS.
• Specify individual advantages and disadvantages.

The continuously increasing number of new psychoactive substances (NPS) available on the drugs of abuse market poses a challenge for clinical and forensic toxicologists. These NPS belong to various chemical classes and only very limited data concerning their safety and toxicokinetic properties are available once they appear on the market. Similar to other xenobiotics, NPS undergo absorption, distribution, metabolism, and excretion processes after consumption. Therefore, the inclusion of metabolites in mass spectral libraries is crucial, especially for urine screening purposes. Authentic human samples may represent the gold standard for identification of metabolites but are often not available and clinical studies cannot be performed due to ethical concerns. However, numerous alternative in vitro and in vivo models are available. The talk will give an overview on selected models, discuss current studies, and highlight recent developments.
 
Biomarkers of antipsychotic-induced metabolic syndrome: Where we stand and where to head to
Hualin Cai, The Second Xiangya Hospital of Central South University, China
 
At the end of this session participants will be able to:

• Summarize new technologies used for biomarker screening of metabolic side effects induced by antipsychotic drugs.
• List different categories of biomarkers reflecting antipsychotic-induced metabolic syndrome and their potential in clinical applications.
• Consider how to extend the mechanism study and find the therapeutic target based on the biomarker information.

Antipsychotic-induced metabolic syndrome (AIMS) presents a significant clinical challenge due to its association with severe somatic disorders, including obesity, dyslipidemia, and insulin resistance, which collectively raise the risk of cardiovascular events and early death. The identification of reliable biomarkers for AIMS is essential for early detection, prevention, and the development of novel personalized treatment strategies. Initially, the presentation will introduce the latest technologies in biomarker screening, emphasizing advancements in genomics, proteomics, and metabolomics that have enabled more precise detection of metabolic disturbances linked to antipsychotic use. We then will provide a comprehensive summary of current biomarkers, categorized by their involvement in key metabolic processes and mechanisms associated with AIMS. These categories include carbohydrate disruption, such as impaired energy metabolism; inflammation and oxidative stress, including mitochondrial dysfunction; dyslipidemia; and gut microbiota dysbiosis. Additionally, we explore how insights from these biomarkers can enhance our understanding of the underlying mechanisms driving these metabolic side effects. This presentation focuses on translating biomarker data into actionable insights, with the goal of identifying novel therapeutic targets. Such targets could lead to more effective interventions that mitigate the metabolic risks associated with antipsychotic treatment. Despite the promise these biomarkers hold, challenges remain and future research should prioritize the validation of these biomarkers in larger cohorts, the integration of multi-omics approaches, and the development of personalized medicine frameworks.
 
How to Write a Paper
Jan-Willem Alffenaar, The University of Sydney, Australia
 
How to Review a paper
Christophe Stove, Ghent University, Belgium
 

Time	Program Outline			Room
0715-0815	Breakfast Roundtables R1701: Discussion & Guide to Implementing a Successful Beta-Lactam Therapeutic Drug Monitoring Program R1703: Unsafeness of uncontrolled, so-called edible cannabinoid products containing HHC: lessons to be learned from recent incidents in Czech schoolchildren and adolescents R1704: Use of the hollow fiber infection model to generate PK-PD targets in humans R1705: Reflections on the use of the direct alcohol biomarker PEth in clinical and forensic toxicology R1706: Personalized medicine substance of use and misuse: the role of clinical laboratories			KC 305
0830-0930	Plenary Presentation: Precision Medicine in Cancer Treatment			KC 101/103/105
0930-1000	Refreshment Break and Exhibit Viewing			KC 201/203/205
1000-1130	Symposium: Clinical Toxicology & Drugs of Misuse	Symposium: TDM in Oncology	Symposium: Immunosuppressive Drugs & Biomarker	Max Bell Bldg
1130-1300	Lunch and Exhibit Viewing			KC 201/203/205
	Industry Workshop: Automated LCMS-Solution Ready for 24/7			KC 303
1300-1430	Oral Presentations			Max Bell Bldg
1430-1500	Refreshment Break and Exhibit Viewing			KC 201/203/205
1500-1630	Symposium: Toxicology & Environmental Health	Symposium: Anti-Infective Drugs	Symposium: TDM of Biologics/ Pharmacometrics	Max Bell Bldg
1630-1730	Poster Viewing			KC 2nd Floor
1730-2200	Congress Dinner at Mount View Barbecue! A truly unique, western Canadian experience!			Offsite

  0715-0815 Breakfast Roundtables   R1701: Discussion & Guide to Implementing a Successful Beta-Lactam Therapeutic Drug Monitoring Program Paul J. Jannetto, Mayo Clinic, USA At the end of this session participants will be able to:

• Identify key stakeholders and champions necessary to successfully implement a TDM program.
• Design a strategy and educational materials to incorporate a beta lactam precision medicine program.
• Summarize the outcomes from setting up a beta lactam program.

In critically ill patients, beta-lactam antibiotics exhibit highly variable pharmacokinetics (PK) which leads to unpredictable therapeutic and toxic effects. Beta-lactam therapeutic drug monitoring (TDM) can improve precision dosing and clinical outcomes, but has not been widely implemented in most hospitals around the world. This roundtable discussion will discuss the practical considerations around implementing a beta-lactam TDM program at one medical center and the organizational infrastructure required, clinical workflows\/tools, educational strategies, and supportive materials necessary for a successful implementation. Data from adult and pediatric ICU patients will be shared from the result of this program. Participants will share and learn various ways to expand TDM programs. R1703: Unsafeness of uncontrolled, so-called edible cannabinoid products containing HHC: lessons to be learned from recent incidents in Czech schoolchildren and adolescents Tesfaye Hundie, Charles University and Motol University Hospital, Czech Republic At the end of this session participants will be able to:

• Discuss the potential risk of substances found over the counter especially in children, where designs are attracting in this age group.
• Enhance developing early warning strategy locally.
• Provide ideas towards developing online quality analytical facilities.
• Enhance organizing all stakeholders’ cooperation to prevent fatal outcomes caused by substance abusers.

This roundtable discussion will: 1. Describe challenges and main pitfalls associated with methodology of substance analysis and both pre-analytical and post analytical errors leading to misleading interpretations. 2. Point out potential drug/food interactions. 3. Propose possibilities of narrowing gaps in management and regulation of abuse able substance and early detection methods. 4. Point out steps to do better aiming improve the state of the art by reaching consensus. Hexahydrocannabinol (HHC), is synthetic version of tetrahydrocannabinol (THC) gained by hydrogenation of parent THC. Both benefits and hazards of HHC are not well studied although unpublished incidents showed that it is not safe–enough. The legal status of HHC varies between countries across the world. This contribution is to involve discussion on the state of the art based on reported incidents in Czech Republic, leading to ban HHC since 1.3.2024 putting the country on the list of European countries banning HHC. The outcomes of the discussion is aiming to make some kind of consensus at list within the IATDMCT society leading to disseminations of the facts further to relevant bodies to avoid the dangers following the abuse substances. R1704: Use of the hollow fiber infection model to generate PK-PD targets in humans Michael Neely , University of Southern California, USA At the end of this session participants will be able to:

• Describe how the hollow fiber infection model (HFIM) works.
• Describe the role of the HFIM in setting breakpoints.
• Discuss modeling approaches to single and combination therapy in the HFIM.
• Explain the contribution of the HFIM to clinical dosing of antimicrobials.

This is a round table discussion to familiarize participants with the use of the HFIM to optimize dosing of anti-infective drugs. R1705: Reflections on the use of the direct alcohol biomarker PEth in clinical and forensic toxicology Christophe Stove, Ghent University, Belgium At the end of this session participants will be able to:

• List the options for direct biomarkers for alcohol use exist and in which matrix they can be monitored.
• Explain how phosphatidylethanol 16:0/18:1 (PEth) is formed and what its kinetics of disappearance are.
• Explain how PEth monitoring can be used to demonstrate (absence of) abstinence.
• Discuss what the possibilities and limitations of PEth monitoring are, in clinical and forensic toxicology.
• Summarize the ISO17025-accredited workflow that has been used for several years now at the Laboratory of Toxicology at Ghent University.

Phosphatidylethanol 16:0/18:1 (PEth) is increasingly used as a direct biomarker to monitor alcohol use. This roundtable will start from the basics about alcohol biomarkers and will give the participants an insight into the ins and outs of PEth monitoring, via the ISO17025-accredited workflow followed by the Laboratory of Toxicology at Ghent University. In the presenter’s lab, PEth has now been routinely determined in 10 µl dried blood microsamples for several years, to monitor (absence of) abstinence in thousands of driving license regranting cases, as well as in clinical and forensic toxicology cases. Real-life cases will be used to facilitate interpretation, allowing the participants to fully comprehend the possibilities offered by PEth monitoring. R1706: Personalized Medicine: Dietary Supplements, Medications, Substances of Use and Misuse, Harm Reduction and the Role of the Clinical Laboratory Manuela Neuman, University of Toronto, Canada At the end of this session participants will be able to:

• Recognize the ongoing demand for education about personalized medicine, as well as personalized diets.
• Discuss the clinical and economic value of using immunogenetic markers of toxicity of therapeutics and dietary supplements.
• Explain the benefits of the use of healthy dietary supplements in individuals that do not use drugs of misuse.
• Distinguish harm reduction strategies in diminishing the negative consequences of possible hypersensitivity syndrome reactions by using the clinical laboratory specific tests.
• Educate patients and their clinicians on how to promote and advocate for toxicity awareness.

This roundtable promotes the adoption of personalized medicine concepts to benefit patients and the health care system. Personalized medicine helps physicians to use diagnostic tests to determine which medical treatments will work best for each patient. Natural products, or even dietary supplements, can interact with medication(s), producing an adverse reaction for a specific individual. By combining data from those tests with an individual’s medical history, health care providers can develop targeted treatment and prevention plans. The treatment and/or enforcement strategies do not eliminate individual hypersensitivity, however, prevention is possible. Therefore, several harm reduction strategies have been sought in order to diminish the negative consequences associated with hypersensitivity. In this roundtable I will present aspects of harm reduction and focus on those innovative strategies. We, at In Vitro Drug Safety and Biotechnology, aim to provide dietary supplement users with information on the composition or potency of the substances they are using in order to raise awareness, decrease exposure to toxic products and ultimately protect the public. The potential involvement of clinical laboratories specialized in drug and dietary supplements will be presented. Examples of substances received at the laboratory and the results of testing will be discussed in the context of clinical symptoms. Another aspect of personalized medicine are idiosyncratic reactions that patients encounter after using therapeutics or herbal and alternative medicines. Drug-induced liver disease and herbal-induced liver injury cause significant morbidity and mortality in patients worldwide. Drug-induced hepatic reactions may produce sufficient hepatocyte injury to affect large-scale liver functions and to cause jaundice because of impaired bilirubin transport. Serious hepatotoxicity refers here to acute hepatocellular death that requires liver transplant. We present immunotoxicity tests that can be used to distinguish which therapeutic or dietary product led to toxicity. Clinical, biochemical, pathological and immunological data on the role of therapeutics and integrative medicine in toxicity are contemporary issues. This roundtable will explore the most significant trends in laboratory medicine practices, science and policy. The conclusions will guide participants in education and advocacy on personalized medicine in laboratory and clinical practice.   0830-0930 Plenary Presentation Personalized Genomics in Cancer: Real World Experience of the Personalized Oncogenomics Program (POG) in BC Melissa McConechy, McGill University Health Centre, Canada At the end of this session participants will be able to:

• Describe personalized oncogenomics in the context of the BC POG program.
• Summarize the utility of whole genome and transcriptome analysis (WGTA) for personalized oncogenomics.
• Explain how WGTA is aiding clinicians in their clinical care.
• Discuss ongoing research within the POG program using various technology.

The Personalized Oncogenomics (POG) program, based in BC, is a research, prospective clinical trial (NCT02155621) that performs whole genome and transcriptome analysis (WGTA) on high risk, metastatic or advanced cancer patients. This presentation will describe the process of the POG program, focusing on how genomic results are analyzed and reported to the treating clinicians. Specific POG tumour cases will be presented to showcase interesting genomic results that are linked to therapeutic options. Immunotherapy is now being widely used, however there is still an ongoing question of what specific patients may benefit from this therapy. Our group has previously published results that were used to design a specific clinical trial for access to immunotherapy (CAPTIV-8, NCT04273061). This work is ongoing and will be briefly described. In progress research will also be presented including using advanced sequencing technologies such as long read Nanopore sequencing. 1000-1130 Symposium: Clinical and Forensic Toxicology – Hot Topics and Substances Presented by the Clinical Toxicology & Drugs of Misuse Committee Co-Chairs: Eric Franssen, Onze Lieve Vrouwe Gasthuis, Netherlands Loralie Langman, Mayo Clinic, USA Presentations: Suicides using sodium azide and nitrite Karen van den Hondel, Public Health Service Amsterdam, Netherlands At the end of this session participants will be able to:

• Discuss the use of these agents for suicides.
• Explain the detection of these agents.
• Describe the characteristics of users of these agents.

This presentation will provide information about the use of sodium azide and nitrite for suicide (attempts) in the Netherlands. It will give an overview of the characteristics of patients using these agents. The presentation will also show how to detect these agents in blood ante- and postmortem. Ethylglucuronide as biomarker for alcohol abuse: potentials and limitations Cristiana Stefan, The Centre for Addiction and Mental Health, Canada At the end of this session participants will be able to:

• Outline the metabolic pathways for ethylglucuronide formation and elimination.
• Discuss test availability for urine ethylglucuronide: commercial vs. laboratory-developed.
• Identify at least three clinical and/or forensic settings requiring monitoring for alcohol abstinence with urine ethylglucuronide.
• Discuss the significance of positive results in relation to various cut-off values according to SAMHSA guidelines.
• Recognize the risk for positive urine ethylglucuronide results unrelated to alcohol use.

The toxicity of harmful (excessive) ethanol consumption and its healthcare and economic burden is well established. Biomarkers to rule in or out toxic alcohol consumption, to determine alcohol use or abstinence or to evaluate treatment efforts are essential investigation tools. This presentation focuses on the use of urine ethylglucuronide, a direct ethanol metabolite, as biomarker of recent exposure to alcohol when detected. Several clinical and/or forensic settings require evidence of alcohol abstinence through monitoring with urine ethylglucuronide. Laboratory considerations are discussed for: test availability (commercial vs. laboratory developed) and units of measures; cut-off values to evaluate extraneous vs. intentional exposure to alcohol; potential for result misinterpretation due to risk for post-collection formation of ethylglucuronide or rare causes of endogenous ethanol formation. Relevant case studies from speaker’s consultancy practice or from literature are included. Cytotoxicity Testing of NPS in Clinical Toxicology Lea Wagmann, Saarland University, Germany At the end of this session participants will be able to:

• Explain the importance of cytotoxicity testing.
• List different strategies suitable to study the in vitro cytotoxicity of NPS.
• Specify individual advantages and disadvantages.

In therapeutic drug development, in vitro cytotoxicity testing is crucial and mandatory. This is not the case for non-therapeutic compounds such as new psychoactive substances (NPS). Numerous case reports of intoxications or even deaths after intake of NPS demonstrate their threat on public health. Some reports associated their intake with liver failure, but detailed knowledge about certain cytotoxicity is usually unknown. To reveal such a potential is thus one task in the field of (analytical) toxicology. The knowledge can in turn help to explain outcomes of chronic intake, symptoms in overdose cases, or fatal events associated with NPS abuse. Recent studies investigated single cytotoxicity biomarkers in individual experiments such as cell viability, leakage of lactate dehydrogenase or cell death. To gain a deeper insight into intracellular processes, it may be favorable to monitor multiple parameters using high-content screening assays. The talk will present, summarize, and discuss published studies and strategies related to the cytotoxic potential of non-therapeutic compounds, particularly NPS. 1000-1130 Symposium: Pharmacokinetics and PGX to optimize drug therapy in Oncology Presented by the TDM in Oncology Committee Co-Chairs: Vikram Gota, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, India Dirk Jan Moes, Leiden University Medical Center, Netherlands Presentations: A modeling and simulation based approach for the regulatory approval of a liquid formulation of 6-mercaptopurine Vikram Gota, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, India At the end of this session participants will be able to:

• Design efficient clinical trials for faster regulatory approvals of novel formulations.
• Explain the significance of modeling and simulation in the regulatory approval of new formulations.
• Use modeling and simulation to predict pediatric exposures from adult healthy volunteer pharmacokinetic data.

The presentation will discuss the development of a novel liquid formulation of 6-mercaptopurine for accurate dose titration in children with ALL. Considerations in determining the strength of the formulation given the ‘small for age’ body weight related issues in developing countries will be discussed. The regulatory path from healthy volunteer pharmacokinetic study to the use of modeling and simulation (M&S) to identify an equivalent liquid dose with respect to the solid dosage form will also be discussed. Finally, the use of M&S to predict pediatric exposures from adult healthy volunteer pharmacokinetic data will be elaborated. Thus, the presentation will lay the framework for the use of M&S to achieve faster regulatory approvals of novel formulations to be used exclusively in children. Shifting from I.V. to s.c. administration with biologics in Oncology: PK considerations: clinical perspective Natasha Leighl, Princess Margaret Cancer Centre, Canada Selected Abstract: Improving cost-effectiveness and patient-friendliness: a simulation study of tailored adjuvant durvalumab therapy in non-small cell lung cancer patients Fenna de Vries, OLVG, Netherlands Selected Abstract: Sex-specific effect of GIST patients pharmacogenetic profile for CYP3A5, ABCB1, ABCG2 and SLC22A1/OCT1 on imatinib plasma exposure Eleonora Cecchin, Centro di Riferimento Oncologico di Aviano (CRO), Italy 1000-1130 Symposium: Biomarkers in Solid Organ Transplantation: now and for years to come Presented by the Immunosuppressive Drugs Committee Co-Chairs: Laure Elens, Université catholique de Louvain, Belgium Nuria Lloberas Blanch, IDIBELL Bellvitge Biomedical Research Institute, Spain Presentations: The biomarker toolkit to optimise outcomes for solid organ transplant patients: will pharmacology lead the way? Jana Stojanova, St Vincent’s Hospital Sydney, Australia At the end of this session participants will be able to:

• Describe at least three promising biomarkers for monitoring immunosuppression and graft health in solid organ transplant recipients, including their mechanisms, potential clinical applications, and current level of evidence.
• Compare and contrast the advantages and limitations of promising transplant-related biomarkers for personalizing immunosuppression and improving transplant outcomes.
• Identify key challenges that need to be addressed to enable widespread clinical implementation of biomarker-guided immunosuppression management in transplant recipients.

Optimised therapeutic drug monitoring of immunosuppressants has improved numerous clinical outcomes in solid organ transplantation, including rejection. While this approach is likely sufficient to ensure a successful post-transplant course for most transplant recipients, some patients are vulnerable to under- or over-immunosuppression placing them at higher risk of efficacy or toxicity related adverse outcomes. Additionally, timely detection of graft rejection is crucial to spare significant graft injury. Since the 2000s, several biomarker approaches have shown promise to resolve this gap in transplant care, including some which have received regulatory approval and are commercialised. Clinical pharmacologists, including IATDMCT members, have made substantial contributions to both the discovery and clinical validation in the transplant biomarker space. Despite promise, there are currently no transplant-related biomarkers widely used in the clinic. The challenges that remain include a need for further clinical validation, establishment of optimal monitoring approaches, and evaluation of cost-effectiveness. Consideration of drug exposure will remain an essential aspect of any attempt to address these challenges. Biomarkers of biopsy-proven rejection in pediatric liver transplant and their role in immunosuppression therapy adjustment Guido Trezeguet Renatti, Hospital Garrahan, Argentina At the end of this session participants will be able to:

• Discuss the current landscape of allograft health monitoring in solid organ transplantation.
• Explain the significance of silent alloimmune injury and its impact on long-term transplant outcomes.
• Evaluate and compare the performance of current and emerging biomarkers, and their potential clinical applications.

Over the past decades, remarkable advancements in patient care have led to excellent short-term outcomes in transplant patients. However, long-term outcomes remain compromised by the effects of silent alloimmune injury and the adverse events associated with immunosuppression. In this presentation, we will explore currently used and novel biomarkers of liver allograft injury, focusing on how they can enable cost-effective monitoring of allograft health. This approach could reduce the need for frequent surveillance biopsies by accurately identifying patients with a low likelihood of active allograft injury. Ultimately, the goal of allograft health monitoring is to tailor immunosuppression therapy to individual requirements, thereby enhancing long-term graft function and patient survival. Monitoring Immunosuppression: Can we get closer to the Action-Can we go beyond TDM? Raman Venkataramanan, University of Pittsburgh, USA At the end of this session participants will be able to:

• Evaluate current TDM practice for immunosuppressive drugs.
• Describe potential opportunities to personalize immunosuppressive drugs and improve graft survival.
• Analyze a few approaches that gets us closer to the action-rejection.

Current TDM approaches use measurement of blood/plasma concentrations of drugs at trough or use area under the curve to identify drug exposure and personalize drug dosing. Such an approach assumes identical drug exposure will result in identical clinical outcomes and assumes no pharmacodynamic variability among patients. A combination of markers that incorporate TDM data with pharmacodynamic markers such as IMPDH activity, Pgp genotype may be more valuable. In addition, B-cell IL-10/tumor necrosis factor α ratio seem to predict immunologic reactivity and clinical outcomes in kidney and liver transplantation. This may identify patients who require more immunosuppression and provide mechanistic insights into selection of therapies to personalize immunosuppression. Additional biomarkers with potential for improving graft outcomes will also be discussed. 1600-1730 Symposium: Toxicology & Environmental Health Presented by the Toxicology & Environmental Health Committee Chair: Souleiman El Balkhi, University of Limoges, France Presentations: The Impact of Environmental pollution to Antimicrobial Agents on Medical Resistance Jana Stojanova, St Vincent’s Hospital Sydney, Australia At the end of this session participants will be able to:

• Identify and explain the major sources of antimicrobial pollution in the environment.
• Compare and contrast the unique considerations and implications that environmental exposure has on resistance for different antimicrobial classes.
• Outline at least three key areas for future research and action in addressing antimicrobial pollution.

Antimicrobial pollution makes a substantial contribution to the significant global problem of antimicrobial resistance. Major sources of contamination include pharmaceutical manufacturing, agricultural practices, healthcare facilities, and domestic use. Environmental exposure patterns have changed over time, often in response to initiatives aimed at mitigating use and disposal. Unfortunately, several areas of particular concern have not been addressed, while others are becoming recognised as a growing problem relatively recently. The impact that environmental antimicrobial exposure has on resistance varies between antimicrobial classes, however the implications on human health are important regardless of drug class. Glyphosate: The Eternal Debate and EFSA’s Reliance on Regulatory Findings Souleiman El Balkhi, University of Limoges, France At the end of this session participants will be able to:

• Discuss the key controversies surrounding the use of glyphosate in agriculture, including the scientific, regulatory, and public health perspectives.
• Evaluate the role of the European Food Safety Authority (EFSA) in assessing the safety of glyphosate, particularly how it integrates and relies on regulatory findings from various sources.
• Critically assess the scientific methodologies and data interpretations used in glyphosate risk assessments, comparing industry-sponsored studies with independent research.
• Formulate informed opinions on the ethical and scientific considerations in the regulation of pesticides like glyphosate, incorporating a balanced view of the ongoing debate.

This presentation, will examine the ongoing controversy over glyphosate’s safety and the role of the European Food Safety Authority (EFSA) in its regulation. Participants will explore the differences between industry-funded and independent research, and how EFSA’s reliance on regulatory findings impacts public health and environmental policy. The session will provide the different views of the scientific and ethical challenges in glyphosate regulation, equipping attendees with the knowledge to engage in informed discussions. Per- and Polyfluoroalkyl Substances (PFAS): An Old Danger and a New Threat? Nolwenn Noisel, University of Montreal, Canada At the end of this session participants will be able to:

• Cite the most common health effects of PFAS.
• Evaluate the public health impact of PFAS exposure.
• Identify vulnerable populations and determinants of exposure.
• Discuss the use of biomonitoring and risk analysis strategies.

The presentation will aim to provide an overview of the most recent knowledge on PFAS. A definition and the main classifications will be presented first, followed by a mention of the primary health effects. The focus will then shift to vulnerable populations and those particularly exposed, such as children and certain workers like firefighters. Finally, PFAS biomonitoring strategies will be discussed, along with their usefulness in risk analysis and public health management. 1600-1730 Symposium: Dish of the Day Presented by the Anti-Infective Drugs Committee Chairs: Sophie Stocker, University of Sydney, Australia Presentations: Fluconazole – the last azole to optimize? Isabel Spriet, University Hospitals Leuven, Belgium At the end of this session participants will be able to:

• Explain the pharmacokinetics of fluconazole.
• Discuss the need for dose optimization of fluconazole.
• Apply dose optimization for fluconazole in obese patients.

This case describes a female obese patient admitted in the hospital for major abdominal surgery. Postoperatively, fluconazole needs to be started as treatment for invasive candidiasis. You are called by the surgeon to advice on the dose – which factors do you take into account? Do you recommend weight based dosing or a higher fixed dose, should this be applied on both loading and maintenance dose? Would you recommend TDM? Or are echinocandins preferred in this situation? Navigating the beta-lactam therapeutic window Rekha Pai Mangalore, Alfred Health/Monash University, Australia At the end of this session participants will be able to:

• Reflect on challenges in recognising neurotoxicity.
• Discuss management of neurotoxicity.
• Explain the importance of individualised dosing.

The speaker will present a series of cases which will highlight the role of individualised dosing of beta-lactams. Catching the Culprit: Benzylpenicillin Neurotoxicity Confirmed by TDM in a Critically Ill Patient With CVVH Maaike Sikma, Utrecht University, Netherlands At the end of this session participants will be able to:

• Interpret benzylpenicillin blood concentrations in relation to neurotoxicity.
• Improve individualized dosing of benzylpenicillin in a critically ill patient with renal dysfunction.
• Recognize neurotoxicity of benzylpenicillin.

This presentation is about a case of a 65-year-old patient who was treated with high-dose benzylpenicillin for severe invasive pneumococcal pneumonia, complicated by acute renal failure managed with continuous venovenous hemofiltration. After cessation of CVVH, the patient experienced multiple tonic–clonic seizures. Therapeutic drug monitoring revealed high total serum concentrations of benzylpenicillin, identifying it as the likely cause of the neurotoxicity. This case study presents the first documented total serum benzylpenicillin concentration associated with neurotoxicity. Vancomycin dosage optimization for pediatric patients with special disease conditions Yuko Shimamoto, National Cerebral and Cardiovascular Center, Japan At the end of this session participants will be able to:

• Explain the effect of growth and development of organ function on PK in children.
• Implement changes in vancomycin PK in children with special disease conditions.
• Consider the patient’s age and medical conditions to adjust the vancomycin dosage.

Providing safe and effective drug therapy to infants and young children requires consideration of the growth and development (maturation) of organ function. The pediatric vancomycin (VCM) dosage recommended by the Infectious Diseases Society of America (IDSA) guidelines is 60-80 mg/kg/day when targeting an AUC/MIC ratio of 400-600. However, this dosage frequently results in underexposure in children with febrile neutropenia (FN) and overexposure in children with critical congenital heart disease (CCHD). This presentation highlights how the augmented renal clearance (ARC) and delayed maturation of renal function impact the optimal dosing of vancomycin in pediatric patients with FN and CCHD, respectively. Non-renal augmented clearance of linezolid Jana Stojanova, St Vincent’s Hospital Sydney, Australia At the end of this session participants will be able to:

• Recognize the potential for extremely high linezolid clearance in critically ill patients with acute lung injury or ARDS, necessitating higher than standard dosing to achieve therapeutic concentrations.
• Distinguish between augmented renal clearance and non-renal clearance mechanisms as causes of increased antibiotic elimination in critically ill patients.
• Explain the proposed role of CYP2J2 induction in the lungs as a novel mechanism for increased linezolid metabolism during acute respiratory illness.

This case is of a young male patient with severe MRSA pneumonia and empyema, requiring twice the recommended linezolid dose for adequate drug exposure. Urine concentration measurement revealed renal clearance is a minor contributor to total clearance. Recent experimental data supports an unusual and transient metabolic induction scenario. 1600-1730 Symposium: TDM of Biologics/ Pharmacometrics Presented by the TDM of Biologics and Pharmacometrics Committees Co-Chairs: Anders Åsberg, Oslo University, Norway Iris Minichmayr, Medical University of Vienna, Austria Dirk Jan Moes, Leiden University Medical Center, Netherlands Annick de Vries, Sanquin Diagnostic Services, Netherlands Presentations: From Theory to Action: Applying MIPD Tools in Clinical Practice Iris K. Minichmayr, Medical University of Vienna, Austria At the end of this session participants will be able to:

• List the advantages and challenges of model-informed precision dosing (MIPD) compared to traditional therapeutic drug monitoring (TDM) of biologics.
• Describe key factors critical for the successful implementation of MIPD in clinical practice.
• Summarize the workflow of applying MIPD for biologics using a clinical decision support tool.

This session will explore model-informed precision dosing (MIPD) and its potential to enhance therapeutic drug monitoring (TDM) for biologics. Key concepts of MIPD will be discussed, together with its advantages over traditional methods and important considerations for successful implementation. A practical case study will illustrate the workflow of MIPD using a clinical decision support tool. Furthermore, recent evidence supporting MIPD in optimizing biologic therapies will be reviewed. Modelling based on real life data; does one model fit all biologics? Stephan van den Berg, Sanquin Diagnostic Services, Netherlands At the end of this session participants will be able to:

• Explain the similarities in the pharmacokinetics of biologics.
• Discuss caveats and importance of decisions in the modeling process of biologics.
• Adopt suitable alternatives when handling sparse data to enhance the reliability of models beyond the fitted population.

Biologics are crucial in treating diseases like oncology, hematology, infectious diseases, and autoimmune conditions. There are 173 therapeutic monoclonal antibodies (mAbs) approved as of May 2023. Understanding a drug’s pharmacokinetic (PK) profile is vital for assessing its safety, efficacy, and dosing. mAbs display high inter-individual variability, which should be considered to ensure sufficient drug exposure for all patients. However, sparse real-world data often leads to unrealistic physiological parameters in PK models. As biologics are similar in size, shape and elimination route, we hypothesized that one base population PK model could rule all PK models. Therefore, we aimed to determine whether population PK models described in literature demonstrate consistent PK parameters across mAbs. Here we show our key findings, caveats of the modeling process, and a proposal for a top-down approach to improve models. This would also enhance the reliability of models beyond the fitted population. Selected Abstract: Monitoring The Biotransformation of Etanercept in the Body Using LC-MS/MS Sho Masui, Keio University, Japan Selected Abstract: Therapeutic drug monitoring of bevacizumab in Hereditary Hemorrhagic Telangiectasia Olivier Le Tilly, Tours University Hospital, France

Time	Program Outline			Room
0800-0900	Committee Meetings
	Clinical Toxicology/Drugs of Misuse Committee			MB 251
	Immunosuppressive Drugs Committee			MB 252
	Pharmacometrics Committee			MB Auditorium
	TDM in Oncology Committee			MB 253
0900-1000	Committee Meetings
	Alternative Sampling Strategies Committee			MB 251
	Anti-Infective Drugs Committee			MB 252
	Pharmacogenetics Committee			MB Auditorium
	TDM of Biologics Committee			KC 305
	Toxicology and Environmental Health Committee			KC 204
	Communications Committee			MB 253
1000-1130	Symposium: Anti-Infective Drugs / Pharmacometrics	Symposium: TDM of Biologics/ TDM in Oncology	Symposium: Regional Asia Pacific Section Symposium	Max Bell Bldg
1130-1300	Lunch and Exhibit Viewing			KC 201/203/205
	Industry Workshop: Therapeutic Drug Monitoring in Psychiatry – Positive impact on patients through lab-clinician collaboration			KC 303
1300-1430	Workshop: Clinical Toxicology & Drugs of Misuse – Bring your own cases	Symposium: Joint Symposium with ACCP	Symposium: Communications Committee Symposium	Max Bell Bldg
1430-1500	Closing Ceremony and Oral & Poster Awards			KC 101/103/105

 
 
1000-1130 Symposium: Children are not small adults: paving the road to PK/PD dose optimization of anti-infectives in children
Presented by the Anti-Infective Drugs Committee
Co-Chairs:
Pieter de Cock, Ghent University, Belgium
Iris Minichmayr, Medical University of Vienna, Austria
 
Presentations:
 
Precision dosing of anti-infectives in children – big solution for small people?
Pieter de Cock, Ghent University, Belgium
 
At the end of this session participants will be able to:

• Describe alterations in PK/PD of anti-infectives in children.
• Relate strategies for improving antibiotic dosing.
• Summarize pitfalls and challenges of different dose optimization strategies.

This session will discuss PK/PD differences between adults and children and extrapolation scenarios. The presentation will include challenges, opportunities and benefits of therapeutic drug monitoring and model-informed precision dosing in children.
 
Use of Physiologically-Based Pharmacokinetic Modelling To Support Antimicrobial Dose Optimization in Children
Samuel Dubinsky, University of Waterloo School of Pharmacy, Canada
 
At the end of this session participants will be able to:

• Describe the basic principles of physiologically-based pharmacokinetic (PBPK) modelling and its application in pediatrics.
• Recognize specific cases where PBPK modelling may support pharmacotherapy in children.
• Discuss future directions in PBPK that could further enhance antimicrobial dose optimization in children.

In this presentation, the speaker will discuss basic principles in PBPK and its use in pediatrics. He will provide specific examples of how PBPK may assist in advancing pharmacotherapy in children receiving antimicrobials. Finally, he will discuss current research gaps and future directions where PBPK may serve as a resourceful tool.
 
Implementing model-informed precision dosing of antibiotics at Cincinnati Children’s Hospital Medical Center
Sonya Tang Girdwood, Cincinnati Children’s Hospital Medical Center, USA
 
At the end of this session participants will be able to:

• Describe the beta-lactam model-informed precision dosing service at Cincinnati Children’s Hospital Medical Center.
• Name some challenges in implementing an antibiotic precision dosing service.
• Recognize patient scenarios that may benefit from model-informed precision dosing.

In this presentation, the speaker will describe the model-informed precision dosing service for beta-lactam antibiotics that was recently launched at Cincinnati Children’s. She will provide details of the work-flow and the challenges in launching a service. She will also provide example(s) of patients who may benefit from this service.
 
Hybrid use of machine learning and population PK/PD to optimize anti-infectives dosing in children
Wei Zhao, Shandong University, China
 
At the end of this session participants will be able to:

• Discuss the population PK and machine learning.
• Describe how to combine the two methods in PK analysis.
• Explain how to use the two approaches to optimize dosing in children.

Children are in a continuous and dynamically changing state of growth and development. Marked differences in the pharmacokinetic and pharmacodynamic behavior of many drugs are reported between children and adults due to the developmental changes in physiological parameters during childhood. The lack of pediatric clinical trial data directly results in the variation and uncertainty of drug therapy in pediatric clinical practice. The urgent need to improve pediatric drug therapy has been recognized by regulators and public health professionals. There has been a growing interest in exploring innovative methodology to optimize pediatric drug development. In this context, pharmacometrics presents a promising and valuable approach. Pharmacometrics is the science of quantitative pharmacology. In application to pediatrics, it involves primarily developmental pharmacokinetic and pharmacodynamic modeling and simulation, which can combine information from many diverse sources as drug characteristics, developmental clinical pharmacology, physiological changes during childhood, pediatric disease and statistics. This presentation will use cases studies to demonstrate how to apply modeling and simulation in optimization of pediatric clinical trial and personalization of drug therapy.
 
 
1000-1130 Symposium: TDM of Biologics/ TDM in Oncology
Presented by the TDM of Biologics and TDM in Oncology Committees
Co-Chairs:
Vikram Gota, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, India
Dirk Jan Moes, Leiden University Medical Center, Netherlands
 
Presentations:
 
Model informed (precision) dosing of Antibody Drug Conjugates in (hemato)oncology
Dirk Jan Moes, Leiden University Medical Center, Netherlands
 
At the end of this session participants will be able to:

• Explain the mechanism of action of ADCs and variability in exposure of ADCs.
• Cite examples of several ADCs where the dose can be optimized using model informed precision dosing and their specific challenges.
• Discuss which model informed precision dosing strategies can be used to personalize the dose in order to reduce financial and clinical toxicity.

Antibody drug conjugates (ADCs) represent a ground-breaking new class of anticancer drugs. ADCs combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs. This innovative approach leverages the targeting capabilities of antibodies to deliver cytotoxic payloads selectively to cancer cells and thereby minimizing systemic toxicity and maximizing therapeutic efficacy. Over the past few decades, ADCs have emerged as a promising class of anticancer drugs, with many under research and increasing number of ADCs receiving regulatory approval for the treatment of various cancers. Despite the hope of a “magic bullet”, often toxicity limits the dose before maximum efficacy is reached. A substantial fraction of patients require dose modifications or treatment discontinuation due to intolerable ADC associated toxicity. Toxicity is rarely driven by target expression in healthy tissue is a usually independent of cancer type. Furthermore, high body weight has been associated with increased risk of peripheral neuropathy. Combining therapeutic drug monitoring with PK-PD modelling has opened a new way of dose and therapy optimization called model-informed precision dosing. Model-informed precision dosing (MIPD) is an more advanced quantitative approach focusing on individualized dosage optimization, integrating complex mathematical and statistical models of drugs and disease combined with individual demographic and clinical patient characteristics. In this session challenges and opportunities of MIPD of Antibody Drug Conjugates in (hemato)oncology will be discussed.
 
Selected Abstract: The relationship between the blood trough concentrations of imatinib and the body compositions in patients with gastrointestinal stromal tumors
Yi Zhou, Chongqing Medical University, China
 
 
1000-1130 Symposium: Regional Asia-Pacific Section (RAPS) Symposium
Presented by the Regional Asia-Pacific Section (RAPS)
Co-Chairs:
Debbie Marriott, St Vincent’s Private Hospital, Australia
Sumith Mathew, Christian Medical College Vellore, India
 
Presentations:
 
Vancomycin-Associated Acute Kidney Injury in Indonesia: A Preliminary Study
Jefman Efendi Marzuki HY, Universitas Surabaya; Ubaya Hospital, Indonesia
 
At the end of this session participants will be able to:

• Discuss how Vancomycin is used in hospitals in Indonesia and the prevalence of vancomycin-induced acute kidney injury (AKI) among patients in Indonesia.
• Outline the justification/the rationale for the establishment of TDM service in Indonesia.
• Promote the rational and prudent use of medications.

The presentation will be about the intention to establish the TDM service in Indonesia, a country with almost 300 million of population and more than 3,000 hospitals. We will present the preliminary study about vancomycin used in 5 different hospitals in Indonesia, the prevalence of vancomycin-associated AKI, and the determinants. We will also describe our plan to conduct several studies to support the need for TDM service in Indonesia.
 
Role of Therapeutic Drug Monitoring of Levetiracetam in patients with Augmented renal clearance
Roopali Somani, Nizams Institute of Medical Sciences, India
 
At the end of this session participants will be able to:

• Describe the effect of Augmented Renal Clearance on Levetiracetam Elimination.
• Explain the need for Higher Dosing of Levetiracetam in Traumatic Brain Injury.
• Explain the need for Therapeutic Drug Monitoring of Levetiracetam in patients with Augmented renal clearance.

Currently, Levetiracetam is the drug of choice for seizure prophylaxis in traumatic Brain Injury patients (TBI). As TBI patients are critically ill, it is postulated that 20-65% of these patients have Augmented renal clearance (ARC) and may not achieve target therapeutic serum concentration of levetiracetam as it is renally eliminated. Therapeutic drug monitoring in these patients might help in early recognition and efficient management of these patients.
 
Affordability and accessibility of TDM in India
Smita Pattanaik, Postgraduate Institute of Medical Education & Research (PGIMER), India
 
Vancomycin-associated acute kidney injury in Indonesia: a preliminary study
Rovina Ruslami, Hasan Sadikin Hospital, Indonesia
 
At the end of this session participants will be able to:

• Outline the current use of vancomycin in several hospitals in Indonesia.
• Discuss vancomycin use in hospitals in Indonesia.
• Assess the prevalence of vancomycin-associated AKI in Indonesia.
• Discuss the way forward regarding the appropriate use of vancomycin in Indonesia as the basis of the establishment of TDM service in Indonesia.

In this session, we will start by introducing Indonesia, and the landscape of health facilities (i.e., hospitals and availability of TDM services) throughout Indonesia. We would like to present the result of the preliminary study (retrospective study). In this session, we also would like to share our future plans, including research, to provide a comprehensive foundation for establishing TDM services in Indonesia.
 
 
1300-1430 Workshop: Comprehensive toxicology screening in clinical and forensic toxicology – Bring your own cases
Presented by the Clinical Toxicology & Drugs of Misuse Committee
Co-Chairs:
Eric Franssen, Onze Lieve Vrouwe Gasthuis, Netherlands
Peter Zweipfenning, MVZ Labor Stein, Germany
 
Moderators:
Eric Franssen, Onze Lieve Vrouwe Gasthuis, Netherlands
Daan Huntjens, Amsterdam University Medical Center, Netherlands
Marieke Sturkenboom, University of Groningen, Netherlands
 
At the end of this session participants will be able to:

• Explain comprehensive toxicology screening in clinical and forensic toxicology.
• List novel options for enhanced eliminations in cases of intoxications.
• Discuss unexpected findings in suspected intoxications.

Postmortal toxicology screening, relevant guidelines and interesting cases are presented and discussed. The audience is invited to participate in the discussion and present their own cases and experiences.
 
 
1300-1430 Symposium: Applications of AI to TDM: Joint Symposium with the American College of Clinical Pharmacology (ACCP)
Chair:
Michael Neely, University of Southern California, USA
 
Presentations:
 
Integrating pharmacodynamics and machine learning to predict neutropenia
Jasmine Hughes, InsightRx, USA
 
At the end of this session participants will be able to:

• Explain the strengths and drawbacks of pharmacodynamic approaches for predicting clinical outcomes.
• Explain the strengths and drawbacks of machine learning approaches for predicting clinical outcomes.
• Design a hybrid model that combines pharmacodynamic models and machine learning models.
• Discuss considerations for implementing predictive models in clinical decision-making.

• Neutropenia as a case study for predicting drug-related adverse events.
• Benefits and drawbacks of PKPD approaches and ML approaches for predicting clinical outcomes.
• Development of a hybrid PKPD/ML model.
• Evaluation of the hybrid PKPD/ML model.
• Context of this approach in the broader context of how predictive models can support clinical decision-making and improve patient care.

 
Machine Learning for the therapeutic drug monitoring of immunosuppressive drugs
Marc Labriffe, University of Limoges, France
 
At the end of this session participants will be able to:

• Explain how machine learning (ML) is used to estimate exposure of immunosuppressive drugs (AUCs).
• Discuss the advantages of using ML methods to improve therapeutic drug monitoring.
• Apprehend the limitations of using ML methods and the ways to prevent them.

 
 
1300-1430 Symposium: Future Prospects for Preventive Medicine Applying Pharmacogenomics, Metabolomics, Proteomics, and Microbiome
Presented by the Communications Committee
Co-Chairs:
Ryuji Kato, Osaka Medical and Pharmaceutical University, Japan
Miao Yan, Second Xiangya Hospital of Central South University, China
 
At the end of this session participants will be able to:

• Explain the technique of Next-Generation Sequencing in adjusting dose of Tacrolimus in the context of organ transplantation.
• Discuss the role of Metabolomics and Microbiome as tools for individualized healthcare.
• Discuss the role of damage associated molecular patterns as a predictive biomarker of drug induced liver injury.

This symposium will discuss future prospects for preventive medicine through the application of pharmacogenomics, metabolomics, proteomics and microbiomics.
 
Presentations:
 
Dosing Algorithms for Tacrolimus in the Era of Next-Generation Sequencing
Smita Pattanaik, Post Graduate Institute of Medical Education and Research, India
 
At the end of this session participants will be able to:

• Explain the basis for dosing algorithms for tacrolimus use in the context of organ transplantation, and the steps for the integration into clinical use in patients.
• Discuss devised algorithms in different ethnic settings and the status of their subsequent testing in independent cohort of the population.
• Describe the barriers to the implementation of the algorithms.

Therapeutic Drug Monitoring (TDM) of Tacrolimus has surpassed all other candidate drugs for TDM in terms of the number. As TDM-Therapeutic Drug Monitoring, transitioned from TDM to Therapeutic Drug Management (TDMx), dose prediction for attaining a target concentration has been the most important contribution of the TDM team to delivering precision medicine. Several dosing algorithms have been proposed for (1) starting dose of tacrolimus at/just before transplantation and (2)dose adjustments after transplantation. These algorithms have included an extensive list of possible covariates like body weight, lean body mass, age, eGFR, haematocrit, serum albumin, genotypes (CYP3A5*1,*3,*6; CYP3A4*22 and ABCB1) Only a few of them have attempted to prospectively validate them in an independent cohort. The validation studies have led to mixed results. Some of the studies met with futility in the population with similar ethnicity belonging to a different or even in the same region where the algorithm included population was selected from. A few were able to demonstrate, success in terms of higher proportion of patients in the dosing algorithms predicted starting dose group compared to the conventional body weight based dosing group, though the clinical significance of such benefit is yet to be demonstrated. The algorithm based dosing has not been able to deliver the promise and choice of dosing still remains empirical. This talk will highlight some of the key issues that may be responsible for the shortcoming of the dosing algorithm based dosing. Tacrolimus pharmacokinetics and pharmacodynamics is known to be affected by several pharmacogenomic determinants. With availability of the powerful tools like NGS, which can test for multiple SNPs, it remains to be seen if that can aid in improving our understanding.
 
 
Metabolomics as a promising tool for individualized healthcare
Ofelia Noceti, National Center for Liver Transplantation and Liver Diseases, Uruguay
 
At the end of this session participants will be able to:

• Metabolic Profiles/Pathways: Describe how metabolites are the end products of cellular processes and how their levels can reflect the functional status of an individual’s metabolism, paving the way for the development of targeted therapies.
• Biomarker Discovery: Discuss how metabolomics can identify biomarkers associated with specific diseases, providing insights into early diagnosis, disease progression, and treatment response.
• Personalized Medicine: Explain how metabolomics can contribute to personalized healthcare by tailoring treatment strategies to an individual’s metabolic profile, optimizing drug efficacy, and minimizing adverse effects.
• Nutritional Assessment: Discuss how metabolomics can be used to assess an individual’s nutritional status, identify dietary patterns, and provide personalized dietary recommendations for better health outcomes.

Metabolomics is a field of “omics” research that focuses on the systematic study of small molecule metabolites present in cells, tissues, or biofluids. It aims to identify and quantify all the metabolites in a biological sample to understand the metabolic processes and pathways involved in various physiological and pathological conditions. Metabolomics has the particularity to integrate the relationships form proteome and their upstream counterparts, as well as those coming from the environment. Metabolites can serve as signals to monitor disease development or progression. As a tool for individualized healthcare, metabolomics has the potential to revolutionize the way we approach disease diagnosis, treatment, and prevention.
 
Microbiome and Inflammasome in Gastrointestinal Diseases
Manuela Neuman, University of Toronto, Canada
 
At the end of this session participants will be able to:

• Describe the link between Ulcerative Colitis, Crohn’s Disease and inflammatory chemokines in blood.
• Explain the role of microbiome in inflammatory bowel disease.
• Recognize the role of nutrition in inflammatory bowel disease.
• Distinguish the differences between the inflammatory bowel disease and inflammatory bowel syndrome.
• Explain the role of apoptosis and necrosis as mechanisms of drug resistance.
• Discuss the role of Damage Associated Molecular Patterns, Metabolome and Microbiome as tools for individualized healthcare.

Inflammatory bowel syndrome and inflammatory bowel disease are two different gastrointestinal diseases. At the end of the presentation the audience will be able to distinguish between these diseases, as well as to appreciate the need of personalized laboratory analysis and personalized therapeutic interventions in the gastrointestinal diseases.
 
 
Damage associated molecular patterns as a predictive biomarker of drug induced liver injury
Ryuji Kato, Osaka Medical and Pharmaceutical University, Japan
 
At the end of this session participants will be able to:

• Describe the mechanism of reactive metabolites formation and inflammasome activation by reactive metabolites.
• Explain the inflammasome activation by DAMPs in immune cells.
• Discuss the potential of DAMPs as early biomarkers of IDILI.

Idiosyncratic drug-induced liver injury (IDILI) remains a serious problem; most IDILI is immune-mediated and there is growing evidence that reactive metabolites trigger an immune response. Reactive metabolites directly or indirectly activate inflammasomes in immune cells, causing IDILI. Reactive metabolites cause cellular stress, leading to the release of damage-associated molecular patterns (DAMPs), and DAMPs activate immune cells. A comprehensive analysis is desirable, as there are many other types of DAMPs. If any of them can be used as early biomarkers, they could be applied as predictive markers for the development of IDILI. This symposium will introduce the currently reported DAMPs, including comprehensive analyses, and consider the potential of DAMPs as early biomarkers of IDILI.