Expertise: Drug Interactions, Drug Metabolism, Distribution and Transport, HIV and AIDS, In vitro to in vivo extrapolation, Pharmacokinetics/Pharmacodynamics, Pregnancy and Fetal Pharmacology, Quantitative Targeted Proteomics
Education
- Postdoctoral fellowship, University of California at San Francisco
- PhD, University of Manchester
- BPharm, University of London
Research Interests
- Mechanisms of drug interactions with antiviral drugs
- Impact of efflux and influx transporters (e.g. P-glycoprotein, OATPs) on tissue concentrations, efficacy and toxicity of drugs targeted to the brain or the liver
- Mechanisms of changes in maternal and fetal drug disposition during pregnancy
Current Projects
- In vitro to in vivo extrapolation of transporter mediated clearance. Our in vitro tools are primary cells (e.g. human hepatocytes and transporter-expressing cell lines). Below are specific examples of projects:
- PET Imaging hepatic transporters in humans using 11C-rosuvastatin – The goal of this project is to image the activity of hepatic uptake (e.g. OATPs and NTCP; sinusoidal membrane) and biliary efflux transporters (BCRP, MRP2, P-gp; canalicular membrane) in healthy volunteers. Then, we will determine if the clearance of a drug (e.g. rosuvastatin) via these transporters can be predicted using in vitro data (transfected cell lines or human hepatocytes). If successful, this will be the first proof of concept that hepatobiliary clearance and hepatic concentration of a drug can be predicted in humans using in vitro models.
- To accomplish the above, we are also using quantitative targeted proteomics to determine the expression of transporters in tissues and cells as well as those expressed solely in the cell membrane in primary and transfected cells.
- Prediction of maternal-fetal disposition and exposure to drugs. The physiology and disposition of drugs in pregnant women can differ considerably from men or non-pregnant women. Thus, to appropriately dose pregnant women, it is important to know the changes in clearance of drugs in pregnant women throughout pregnancy. Also, it is important to determine the exposure of the fetus to drugs throughout pregnancy. However, such studies are logistically difficult, impossible or ethically not possible for all drugs administered to pregnant women. Therefore, tools are needed to predict maternal-fetal exposure to drugs. We are developing such tools through studying the disposition of “model’ drugs in pregnant women and then using mathematical models (e.g. PBPK) to predict maternal-fetal exposure to any drug which might be administered to pregnant women. We have already obtained much success in predicting exposure of pregnant women to drugs. Now we are developing mathematical models to predict fetal exposure to drugs. These models will be verified using limited fetal exposure data available at term.
Biography
Dr. Jashvant “Jash” Unadkat is Professor in the Department of Pharmaceutics and joined the department in 1985. He also holds an adjunct appointment in the Department of Anesthesiology and research affiliate appointments with the UW Center for AIDS and STD Research, Washington National Primate Research Center and the Center for Human Development and Disability. He studies the transport and metabolism of HIV and other antiviral drugs. His research into drug transport could potentially lead to better ways to treat diseases such as Hepatitis C, AIDS and Alzheimer’s.
Dr. Unadkat is the 2012 recipient of the American Association of Pharmaceutical Scientists (AAPS) Research Achievement Award in Pharmacokinetics, Pharmacodynamics and Drug Metabolism. He has previously served as associate editor for the “Journal of Pharmaceutical Sciences,” editor of “AAPS Journal,” and a member of the National Institutes of Health Pharmacology study section. He has published more than 170 peer-reviewed research papers and is a fellow of American Association for the Advancement of Science, AAPS, and Japanese Society for the Study of Xenobiotics. He is the founding chair and member of the focus group of AAPS on Drug Transport and Uptake.
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 on drug disposition during pregnancy.” (PubMed.gov)