Effects of the ABCG2 and ABCB1 drug transporter polymorphisms on the pharmacokinetics of bicalutamide in humans

Backgrounds: Bicalutamide is an oral non-steroidal anti-androgen used in the treatment of prostate cancer. Drug transporters P-glycoprotein encoded by ABCB1 and breast cancer resistance protein (BCRP) encoded by ABCG2 are involved in the transportation of bicalutamide and its treatment failure. We evaluated the roles of ABCB1 and ABCG2 genetic polymorphisms in the pharmacokinetics of bicalutamide in humans. Methods: After a single oral dose of 150. mg bicalutamide was administered, plasma concentrations of bicalutamide were measured, and pharmacokinetic analyses were performed in 27 healthy subjects according to ABCB1 (c.1236C. >. T, c.2677G. >. T/A, and c.3435C. >. T) and ABCG2 (c.34G. >. A and c.421C. >. A). Results: ABCB1 polymorphisms did not affect the plasma levels of bicalutamide and the pharmacokinetic parameters did not differ among ABCB1 genotype groups. However, the ABCG2 c.421C. >. A polymorphism significantly influenced the plasma levels and pharmacokinetics of bicalutamide gene dose-dependently. Conclusions: The ABCB1 genetic polymorphisms did not influence the pharmacokinetics of bicalutamide. However, ABCG2 c.421C. >. A significantly and gene dose-dependently influenced its pharmacokinetics, but c.34G. >. A did not.