The Next Frontier in ADME Research: Predicting Tissue Drug Concentrations
Presented by: Jashvant Unadkat, Ph.D., University of Washington
Monday, December 2, 2019
View the Recording View the Slides
Tissue concentrations determine efficacy and toxicity of a drug. Transporter expression at the tissue:blood barrier (e.g. liver:blood or brain:blood barrier) can result in “asymmetry” or disconnect in total (and unbound) tissue:blood concentration at steady-state. Even where transporters are not present at the tissue:blood barrier, dynamic prediction of tissues concentrations is important to predict drug efficacy or toxicity. In humans, except for Positron Emission Tomography (PET) or other imaging methods, it is impossible to measure tissue drug concentrations. For this reason, methods are needed to predict such concentrations and to verify these predictions. Therefore, we developed a proteomics-informed approach to predict tissue drug concentrations (including fetal drug concentrations) through modeling and simulation. In addition, we developed PET imaging methods to measure and verify the model-predicted tissue drug concentrations in humans. Data will be presented to show the promise of this approach. Once our proteomics-informed approach has been verified with additional probe substrates, which interrogate a variety of transporters, it can be used to routinely predict tissue concentration of drugs under development. Supported by UWRAPT, funded (past and present) by Gilead, Takeda, Amgen, Merck, Biogen, Genentech, BMS, and Pfizer.
About the Speaker:
||Jashvant (Jash) Unadkat, Ph.D. is the Milo Gibaldi Endowed Professor at the School of Pharmacy, University of Washington, Seattle. He received his Bachelor degree in Pharmacy (B.Pharm.) from the University of London (1977), his Ph.D. from the University of Manchester (1982; advisor Prof. Malcolm Rowland) and his postdoctoral training at the University of California at San Francisco (1982-85; advisor the late Dr. Lewis B. Sheiner).|
Dr. Unadkat’s research interest is focused on elucidating the mechanisms of transport and metabolism of drugs. In particular his laboratory has been interested in metabolism and transport of drugs during pregnancy, and transport of drugs across the placental, hepatic, intestinal and blood-brain barrier. Dr. Unadkat has published more than 190 peer-reviewed research papers. He is a fellow of AAAS, AAPS, JSSX, and the founding co-chair (1999-2001) of the focus group of AAPS on Drug Transport and Uptake. Dr. Unadkat received the AAPS Research Achievement Award in 2012. Dr. Unadkat created and leads the UW Research Affiliates Program on Transporters (UWRAPT), a cooperative effort between the UW School of Pharmacy and pharmaceutical companies. He also leads UWPKDAP, a NIDA funded Program Project grant (P01) on drug disposition during pregnancy. Dr. Unadkat has been an Associate Editor for the Journal of Pharmaceutical Sciences, an Editor of AAPS Journal, and a member of the NIH Pharmacology study section (2000-3). Dr. Unadkat is currently on the editorial board of J. Pharm. Sci. and the AAPS Journal. Dr. Unadkat has organized or co-organized numerous national and international conferences on the role of transporters and pregnancy in disposition of drugs.