April 16, 2020
Presenter: Jashvant D. Unadkat, PhD, Milo Gibaldi Endowed Professor, Dept. of Pharmaceutics, School of Pharmacy, University of Washington, Seattle
Date: 7 May 2020, 4 pm (GMT)
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.
Previous entry: Meet the Experts Anniversary Symposium Cancellation