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.

Quantitative, Translational, & ADME Sciences (QTAS), Abbvie Inc., North Chicago, IL, USA Abstract: Compounds exhibiting low metabolic clearance are often favored to improve pharmacokinetic profiles and decrease dose. To predict clearance, common experimental techniques include incubations with liver microsomes or cryopreserved hepatocytes in suspension. Hepatocytes in suspension are generally favored as they enable testing of a nearly comprehensive set of metabolic enzymes. However, suspension hepatocytes gradually lose viability in culture, limiting ability to test stable compounds that require longer incubations. Plated hepatocytes will survive for days but lose most drug metabolizing enzyme capacity within 48 hours. In this presentation, methods to overcome loss of phenotype (or increase in assay analytical sensitivity) will be presented. Also, the performance of the models with up to 50 compounds of varying physical chemical properties for predicting clearance will be discussed. The models include hepatocyte suspensions, co-cultures with mouse fibroblasts, tri-cultures with human stromal and endothelial cells, high well density spheroids, and finally a “pre-load” model using mono-culture hepatocytes.

This webinar aims to present novel research on hepatic transport zonation in metabolic dysfunction-associated steatohepatitis (MASH) and the interaction of Δ9-tetrahydrocannabinol (THC) with hepatic and placental transporters, thereby enhancing our understanding of THC disposition in pregnant women. This includes elucidating the identity of transporters influencing the disposition of THC and its metabolites, and the application of a novel liver PBPK model that incorporates zonal distribution of hepatic transporters to predict disease-related changes in statin disposition for patients with MASH.

This webinar is intended to provide drug developers with a comprehensive understanding of the unique DMPK challenges posed by oligonucleotide therapeutics and practical strategies to overcome them. Attendees will gain insights into advanced delivery platforms, customized pharmacokinetic approaches, and specialized administration methods, particularly for CNS-targeting oligonucleotides. By exploring real-world examples and established methodologies, the webinar aims to empower researchers to accelerate preclinical development and enhance their success in drug development and regulatory submissions.

This webinar will introduce dynamic free fraction (fd) as a new concept characterizing drug protein binding and demonstrate the utility of fd in hepatic clearance mediated by CYP and OATP transporter.

This webinar is intended to raise the awareness of complicated scenario where drug-drug-disease interaction occurs and how to evaluate the PK of drugs using PBPK to inform the optimal use of drugs in such patient group.