Written by Bhagwat Prasad, Ph.D.
The University of Washington Research Affiliate program on Transporters (UWRAPT) is a corporate affiliate program of the University of Washington, School of Pharmacy, initiated in 2012 by Prof. Jashvant D. Unadkat. The purpose of this program is to bring together collective expertise and resources from pharmaceutical industry and academia to develop tools to better understand inter-individual variability in pharmacokinetics (PK) of drugs.
Primarily focused on drug transporters, UWRAPT is currently supported by Astrazeneca, Genentech and Merck to fill important knowledge gaps in mechanisms of drug disposition. Together, the four institutions started collaboration on nonproprietary research to help enhance knowledge about the types and levels of transporters expressed in human tissues. Such information is crucial to develop better systems and physiologically based pharmacokinetic (PBPK) models to predict transporter-mediated drug disposition, inter-individual variability in drug disposition and drug interactions. In Year 1, UWRAPT had determined the interindividual variability in protein expression of major hepatic sinusoidal (OATP1B1, OATP1B3 and OATP2B1) and canalicular (P-gp, BCRP and MRP2) transporters in the UW liver bank (n>60). The impact of covariates like age, sex, genotype on the expression of these proteins was also investigated. Key findings of this research include, i) 4-8 fold variability in protein expression of these transporters, ii) genotype dependent expression of OATP1B1, iii) no effect of age and sex on transporter protein expression, and iv) poor (OATP1B3/OATP2B1) or no correlation in the protein expression of these transporters. UWRAPT also supports member companies by quantifying protein expression of transporters of interest in member provided cells or tissue samples.
In Year 2, the proposed work of UWRAPT involves determination of the activity/expression correlation of transporters in transfected cell lines and expression of hepatic transporters in preclinical animals (e.g. mice, rat). In the future, UWRAPT plans to generate comprehensive quantitative information on expression of drug transporters in other human/animal tissues. Once these data are obtained, they can be used to predict disposition and interactions of drugs where transporters are involved. Ultimately, the goal of UWRAPT is to help scientists better predict the fate of new drugs early in development. In turn, this will help develop safe and effective medication for use in the clinic.
For more information about UWRAPT membership (including how to join UWRAPT), collaboration opportunities and UWRAPT publications/abstracts please visit http://sop.washington.edu/uwrapt.
Prasad B, Evers R, Gupta A, Hop CE, Salphati L, Shukla S, Ambudkar S, Unadkat JD
Drug Metab Dispos. 2013 Oct 11. [Epub ahead of print]