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.