Date: June 25 2012
Presenter(s): Dr. Jashvant (Jash) Unadkat, Ph.D.
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.
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.
About the presenter:
Professor of Pharmaceutics in the School of Pharmacy, University of Washington, Seattle, US
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.