The Next Frontier in ADME Science: Predicting and Verifying Tissue Drug Exposure

Date: May 07 2020
Presenter(s): Jashvant D. Unadkat, PhD

Time:

8:00 am (PDT)

11:00 am (EST)

4:00 pm (GMT)

5:00 pm (CET)

6:00 pm (IST)

11:00 pm (Beijing)

12:00 am (Tokyo, Seoul)

Summary:

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 to predict such concentrations and to verify these predictions are needed.  Therefore, we have developed a proteomics-informed approach to predict tissue drug concentrations (including fetal drug concentrations) through modeling and simulation.  In addition, we have 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 by Genentech, Merck, Biogen, Gilead, BMS, Pfizer and Takeda.

Presenter:

Jashvant (Jash) D. Unadkat, Ph.D., Milo Gibaldi Endowed Professor, Dept. of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA

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) and his postdoctoral training at the University of California at San Francisco (1982-85).  Dr. Unadkat studies the mechanisms of transport and metabolism of drugs, including during pregnancy.  Dr. Unadkat has published more than 200 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), funded by pharmaceutical companies and UWPKDAP, a NIDA funded Program Project grant (P01) on drug disposition during pregnancy.