Abstract: AIM: To investigate the effects of the genetic polymorphism of organic anion transporting polypeptide 1B1 (OATP1B1) on the pharmacokinetic profile of repaginide in Chinese subjects. METHODS: The common haplotypes of SLCO1B1 (the coding gene of OATP1B1), which were reported as SLCO1B1 ^* 1a, ^* 1b, ^* 5 and ^* 15, were determined in 16 healthy male volunteers with the genotypes of ^* 1b/^* 1b, ^* 1a/^* 1a or ^* 1a/^* 1b, ^* 1a/^* 15 or ^* 1b/^* 15.A single dose (4 mg) of repaglinide tablets was given orally. The plasma concentrations of repaglinide were determined by HPLC-MS-MS method. The pharmacokinetic parameters were obtained by DAS Ver 2.0.The statistical differences of the pharmacokinetic parameters were assessed by SPSS 12.0.RESULTS: The values of AUC_{0-8 h} of SLCO1B1 ^* 1b/^* 1b, SLCO1B1 ^* 1a/^* 1a or ^* 1a/^* 1b and SLCO1B1 ^* 1a/^* 15 or ^* 1b/^* 15 three groups were (63±20), (70±26) and (82±24) μg·L^-1 ·h respectively. The values of C_max were (56± 16), (52±17) and (58±34) μg/L respectively. There were no significant differences between any two groups. CONCLUSION: The pharmacokinetic profile of repaglinide was affected by the genetic polymorphism of OATP1B1, but the difference from this experiment is not large enough to affect clinical drug safety and effectiveness.

Key words: repaglinide, organic anion transporting polypeptide 1B1, genetic polymorphism, pharmacokinetics