Purpose: To investigate the contribution of the most frequent single nucleotide polymorphism (SNPs) of the organic anion transporting polypeptide 1B1 (OATP1B1) 388A>G to the pharmacokinetics of pitavastatin in Chinese healthy volunteers.
Methods: Eighteen healthy volunteers participated in this study. Group 1 consisted of nine subjects who were of 388AA wild-type OATP1B1 genotype. Group 2 consisted of seven subjects with the 388GA genotype and two 388GG homozygotes. Two milligram of pitavastatin was administered orally to the volunteers. The plasma concentration of pitavastatin was measured for up to 48 h by liquid chromatography-mass spectrometry (LC-MS).
Results: The pharmacokinetic parameters of pitavastatin were significantly different between the two genotyped groups. The concentration (C(max)) value was higher in the 388GA + 388GG group than that in the 388AA group (39.22 +/- 8.45 vs. 22.90 +/- 4.03 ng/mL, P = 0.006). The area under the curve to the last measurable concentration (AUC(0-48)) and area under the curve extrapolated to infinity (AUC(0-infinity)) of pitavastatin were lower in the 388AA group than in the 388GA + 388GG group (100.42 +/- 21.19 vs. 182.19 +/- 86.46 ng h/mL, P = 0.024; 108.12 +/- 24.94 vs. 199.64 +/- 98.70 ng h/mL, P = 0.026) respectively. The oral clearance (Cl/F) was lower in the 388GA + 388GG group than that in the 388AA group (12.46 +/- 4.79 vs. 19.21 +/- 3.74/h, P = 0.012). The elimination of half-life (t(1/2)) and peak concentration times (T(max)) values showed no difference between these groups.
Conclusions: The OATP 388A>G polymorphism causes significant alterations in the pharmacokinetics of pitavastatin in healthy Chinese volunteers and this may well be clinically significant.