The workshop is neither trying to provide a 101 course on LC-MS proteomics nor attempts to focus on what is new in LC-MS proteomics techniques. Attendees need to have some background but not necessarily leading experts in the field. The consensus report from the previous ISSX Workshop held in 2018 (Prasad et al. 2019, Clinical Pharmacology and Therapeutics) is considered a background reading. The recent Symposium Repot from North American ISSX 2023 in Boston (Prasad et al 2024, Drug Metabolism Disposition, In Press) captures the content of lectures and workshop exercises. Hence, the event builds on what is known in the literature in relation to LC-MS proteomics and provides more practical guidance for those who are expanding their research activities in this area, such that they do not go through pitfalls and get to the end point faster.

This webinar will highlight the utility of mechanistic PBPK modeling to not only predict fetal circulatory THC concentrations but also fetal tissue THC concentrations, including in the brain. The approach outlined will provide a blueprint to develop a PBPK model to predict tissue drug exposure in any population. The audience will gain an understanding of how to identify and quantify key pathways involved in driving fetal drug exposure, determine the impact of each pathway, and incorporate them into a PBPK model to predict fetal drug exposure in both the fetal circulation as well as tissues. They will also learn how transcriptomics and proteomics can inform the effects of a drug on molecular signatures within a target tissue such as the brain.

This symposium/webinar is intended to draw attention to our recent findings (in press at Communications Biology) showing that human liver microsomes and recombinant enzymes may misidentify CYP enzymes responsible for metabolism of new drug entities. Given the potential seriousness of the inaccuracies, we would like to share this with the drug metabolism community and regulatory authorities.

Physiologically based pharmacokinetic (PBPK) modelling is an approach that utilizes the knowledge of the physiological and biological elements of the human or animal body, otherwise known as “systems data”, to predict the PK of drugs when used in conjunction with relevant compound or drug data. This involves model development of both the compound and the population of interest in a suitable PBPK platform.

Drug-drug interactions (DDIs) mediated by renal transporters such as OCT2 and MATE1/2K pose significant challenges in drug development and clinical pharmacology. Traditional approaches to assess DDI risk often rely on in vitro inhibition data and clinical studies using probe drugs. However, recent advances, including the use of endogenous biomarkers, extended clearance concepts, and physiologically based pharmacokinetic (PBPK) modeling, offer promising alternatives for early prediction and mechanistic understanding of transporter-mediated DDIs.

This seminar aligns with addressing the questions and concerns early stages of a research career, emphasizing how early investigators craft a coherent scholarly identity while navigating institutional structures, mentorship, and funding ecosystems.

This webinar aims to introduce novel research on emerging transporters and their potential involvement in disease modulation and treatment. This includes characterizing the activity of OCTN1 and LAT1 in the brain and spinal cord, the role of these transporters in influencing the efficacious exposure of ergothionine and pregabalin and their therapeutic effect in preclinical mice models of Alzheimer's Disease and cold allodynia, respectively.