Principles of Transporter Drug Interactions with Special Focus on Hepatic and BBB Transporters

Date: June 25 2012
Presenter(s): Dr. Jashvant (Jash) Unadkat, Ph.D.

Principles of Transporter Drug Interactions with Special Focus on Hepatic and BBB Transporters

Webinar presented on June 25, 2012, by Professor Jashvant (Jash) Unadkat, Ph.D.

(Dept. of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA)

Transporters are involved in clinically significant drug-drug interactions (DDI). Such interactions can occur at multiple sites, including in organs important in drug absorption (e.g. intestine), elimination (e.g. liver and kidneys) and distribution (e.g. brain). Notably, some of these interactions can be “hidden”, occurring in a tissue with no discernible trace in the systemic circulation. In addition, for drugs that are both transported and metabolized, DDI will most prominent when they occur at the “rate-limiting step” in the clearance of the drug. Thus, identifying this step is important for predicting such DDI. To illustrate such interactions, I will focus my presentation on clinically relevant DDI at these sites, involving P-glycoprotein, OATPs, and other transporters. IVIVC of these interactions will also be addressed. P-glycoprotein based DDI at the human blood-brain barrier, measured by PET imaging, will also be discussed. This webinar will help you make decisions about when to be concerned about DDI during the drug development process.

Prof. Jashvant (Jash) D. Unadkat

Jashvant (Jash) Unadkat, Ph.D. is a Professor of Pharmaceutics in the School of Pharmacy at the University of Washington, Seattle. He received his Bachelor's 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’s research interests are focused on elucidating the mechanisms of transport and metabolism of anti-viral and anti-cancer drugs. In particular his laboratory has been interested in metabolism and transport of drugs during pregnancy, and transport of drugs across the placental, intestinal and blood-brain barrier. Dr. Unadkat heads up a program (UWRAPT) funded by a consortium of pharmaceutical companies to quantify the expression of transporters in human tissues. Dr. Unadkat has published more than 140 peer-reviewed research papers. He is a fellow of the AAAS, AAPS, JSSX, and the founding member and the past chair (1999-2001) of the focus group of AAPS on Drug Transport and Uptake. 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. He has organized or co-organized numerous national and international conferences on the role of transporters and pregnancy in disposition of drugs.

Literature References provided by Prof. Unadkat (1) Sasongko et al., Clin Pharmacol Ther. 2005 77:503. (2) Hsiao et al., J Pharmacol Exp Ther 2006 317:704-710. (3) Eyal et al., J Nucl Med. 2009 50:798. (4) Hsiao P, et al., Drug Metab Dispos. 2008 36:481. (5) Muzi et al., J Nucl Med. 2009 50:1267. (6) Chung et al., Br J Pharmacol. 2010 159:394. (7) Eyal et al., Pharmacol Ther. 2009 123:80. (8) Eyal et al., Clin Pharmacol Ther. 2010 87:579. (9) Unadkat JD et al., In Pang KS, Rodriques AD, and Peter RM (eds), Enzyme-and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges. Springer, New York, 2010. pp. 517-553. (10) Endres CJ, Endres MG, Unadkat JD. Interplay of drug metabolism and transport: a real phenomenon or an artifact of the site of measurement? Mol Pharm. 2009 Nov-Dec;6(6):1756-65.