¹Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

Correspondence: M Niemi, (mikko.niemi@helsinki.fi)

Received 28 January 2008; Accepted 29 February 2008; Published online 16 April 2008.

Abstract

In a randomized crossover study, 24 SLCO1B1-genotyped healthy volunteers were given daily doses of 1,200 mg gemfibrozil, 40 mg atorvastatin, or placebo, followed by 0.25 mg of repaglinide on day 3. The mean increase in the repaglinide area under the plasma concentration–time curve from 0 h to infinity (AUC_0–) produced by gemfibrozil was larger in individuals with the SLCO1B1 c.521CC genotype (n = 6) than in those with the c.521TC (n = 6) and c.521TT (n = 12) genotypes, by factors of 1.56 (P = 0.004) and 1.54 (P = 0.002), respectively. Gemfibrozil prolonged the repaglinide elimination half-life 1.43 times more in the c.521CC group than in the c.521TT group (P = 0.047), but no differences were seen in the effects on peak plasma concentration (C_max). While on gemfibrozil, the minimum blood glucose concentration after repaglinide intake was 19% lower in the c.521CC participants than in the c.521TT participants (P = 0.009). In the c.521TT group, atorvastatin intake had the effect of increasing repaglinide C_max and AUC_0– by 41% (P = 0.001) and 18% (P = 0.033), respectively. In conclusion, the extent of gemfibrozil–repaglinide interaction depends on SLCO1B1 genotype. Atorvastatin raises plasma repaglinide concentrations, probably by inhibiting organic anion transporting polypeptide 1B1 (OATP1B1).