No significant effect of SLCO1B1 polymorphism on the pharmacokinetics of rosiglitazone and pioglitazone

AIMS To examine possible effects of polymorphism in the SLCO1B1 gene, encoding the hepatic uptake transporter organic anion transporting polypeptide (OATP) 1B1, on the pharmacokinetics of rosiglitazone and pioglitazone in a prospective genotype panel study. METHODS Sixteen healthy volunteers with the homozygous SLCO1B1 c.521TT genotype (controls), 12 with the heterozygous c.521TC genotype and four with the homozygous c.521CC genotype ingested a single 4-mg dose of rosiglitazone and a single 15-mg dose of pioglitazone in a cross-over study with a wash-out period of at least 1 week. RESULTS SLCO1B1 polymorphism had no statistically significant effect on any of the pharmacokinetic variables of rosiglitazone, pioglitazone or their metabolites. The mean +/- SD area under the plasma rosiglitazone concentration-time curve from time 0 to infinity (AUC(0-infinity)) was 2024 +/- 561 ng ml(-1) h in the c.521TT subjects, 1763 +/- 288 ng ml(-1) h in the c.521TC subjects (geometric mean ratio c.521TC/c.521TT 0.89; 95% confidence interval 0.72, 1.11) and 1729 +/- 346 ng ml(-1) h in the c.521CC subjects (c.521CC/c.521TT 0.87; 0.63, 1.20). The AUC(0-infinity) of pioglitazone averaged 6244 +/- 1909 ng ml(-1) h in the c.521TT subjects, 5123 +/- 1165 ng ml(-1) h in the c.521TC subjects (c.521TC/c.521TT 0.83; 0.65, 1.06) and 4851 +/- 1123 ng ml- 1 h in the c.521CC subjects (c.521CC/c.521TT 0.79; 0.55, 1.14). There was a significant correlation between the AUC(0-infinity) of rosiglitazone and pioglitazone (r=0.717, P < 0.001). CONCLUSIONS The SLCO1B1 c.521T -> C SNP does not affect the pharmacokinetics of rosiglitazone or pioglitazone, indicating that OATP1B1 plays no significant role in the disposition of these drugs.