Ethnic variability in the pharmacokinetics of organic anion-transporting polypeptide (OATP) 1B1 substrates has been observed for some drugs, but the basis of the differences has been unclear. A previous hypothesis proposing intrinsic ethnic variability in activity was inconsistent with data collected from compounds that are OATP1B1 substrates but not breast cancer resistance protein (BCRP) substrates (e.g., pitavastatin and repaglinide).

We evaluated an alternative hypothesis for ethnic variability in the pharmacokinetics of transporter substrates based upon allelic frequencies of both OATP1B1 and BCRP. Simulations based on this hypothesis can reasonably describe OATP1B1 or BCRP genotyped pharmacokinetic time course data in Caucasian, Chinese, Japanese, and Korean populations.

The hypothesis and mathematical model developed in this study provide insights into the sources of ethnic variability and provide a foundation for prospectively predicting ethnic variability in the pharmacokinetics of transporter substrates.