Trending Topics in ADME & Drug Development Research: Novel methodologies to improve IVIVC

Speaker: Dr. Brian Ogilvie, Vice President, Scientific Consulting, BioIVT

Abstract: The ICH M12 Guideline was finalized on May 21st, 2024, after extensive review of industry and other comments.  The Guideline is the culmination of the extensive work by the Expert Working Group. The Expert Working Group was formed in 2018 and is a committee of experts charged with harmonizing member regulatory agencies’ guidelines to create a single guideline that will be used across all member countries.  The new Guideline replaces the corresponding drug interaction guidance documents from the US FDA, EMA, and PMDA, among others.

Speaker: Dr. Ayman El-Kattan, Ph.D. President of EPA Consulting Services

Abstract: Drug intestinal secretion is a frequently overlooked yet vital route of drug elimination, characterized by the active transport of drugs from the bloodstream into the intestinal lumen. This presentation aims to provide a comprehensive exploration of the mechanisms driving drug intestinal secretion, highlighting the physicochemical properties that influence this process and its relevance within the Extended Clearance Classification System (ECCS).
We will identify and discuss the key intestinal transporters involved in this elimination route, such as P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), and examine how these transporters facilitate the movement of drugs into the intestinal lumen. The presentation will also delve into the potential impacts of drug-drug interactions and food effects on the pharmacokinetics of compounds, particularly focusing on how these factors can alter the oral exposure and overall drug efficacy.
Furthermore, we will outline various methodologies to identify and investigate this elimination route, utilizing in silico models, in vitro assays, and in vivo preclinical studies. These approaches will be discussed in detail to provide a robust framework for researchers to study drug intestinal secretion effectively.
By shedding light on this critical elimination pathway, we aim to underscore its significance in the broader context of pharmacokinetics and drug development. This presentation advocates for increased attention and research into drug intestinal secretion, emphasizing its potential impact on drug safety, efficacy, and overall therapeutic outcomes.

Speaker: Dr. Mark Warren, Senior Director of Transporter Services, BioIVT

Abstract: Excipients are “inactive” ingredients that are added to therapeutic drug products that are not intended to exert therapeutic effects by themselves. However, these excipients may inhibit intestinal transporters that can be responsible for enhancing or reducing the absorption of not only the drug that is administered along with the excipient, but also the absorption of co-medications that have never been tested with that excipient. Generic products may contain different excipients than the original branded medication, which may also contribute to unexpected drug-drug interactions. Numerous excipients were tested and shown to inhibit OATP2B1, an intestinal drug uptake transporter, as well as BCRP and P gp, intestinal drug efflux transporters.

Speaker: Dr. Bhagwat Prasad, Professor of Pharmaceutical Sciences, Washington State University

Abstract: Understanding enzyme and transporter distribution in liver subcellular compartments is crucial for drug metabolism and toxicity studies. This study uses global quantitative proteomics to analyze human liver lysosomal (HLL) and microsomal (HLM) preparations. From 13 individual donors, 2000-2500 proteins were consistently detected in both HLL and HLM. Lysosomal markers (HEXA, HEXB, ACP2) were abundant in HLL, while enzymes like CYPs and UGTs were ~50-60% in HLL compared to HLM. Notably, hydrolases and transporters such as OATPs, OCT1, and ABC transporters were enriched in HLL. These findings are vital for developing liver-based in vitro tools and understanding drug interactions.

Speaker: Dr. Tina Mueller, Scientific Advisor, ADMET Services, BioIVT

Abstract: There is renewed interest in developing psychedelics such as psilocybin, LSD or MDMA as potential treatments for mental health disorders including major depression, post-traumatic stress disorder, and anxiety. This presentation will explain the different types of psychedelics that are being investigated as potential drugs, provide an overview of their long history of use and give insights into the market. In the second part, we will present current efforts to bring these potential drugs to the clinic with an emphasis on the pharmacology and current understanding of the mode of action as well as the ADME properties of these compounds. Lastly, we will briefly touch on potential challenges.