The Effects of Simvastatin on the Pharmacokinectics of Sitagliptin

摘要

Background Treatment with the combination of sitagliptin (a dipeptidyl peptidase 4 inhibitor which improves glycemic control) and simvastatin (a well characterized lipid-lowering agent) may be considered an appropriate approach to management of type 2 diabetes and its associated increased risk of cardiovascular disease. Objective An investigation of the effects of simvastatin on the pharmacokinetics of sitagliptin was conducted. Methods Ten healthy men and women were enrolled into an open-label, randomized, 2-period, crossover study. Pharmacokinetics of sitagliptin were measured after a single dose of sitagliptin 100-mg alone, and after a single dose of sitagliptin 100-mg administered on Day 5 of a 7 day course of simvastatin 80-mg once daily. Results The geometric mean ratio of (sitagliptin + simvastatin) / sitagliptin and corresponding 90% confidence interval for sitagliptin AUC 0-∞ and C max were 1.01 (0.97, 1.05), and 1.12 (1.00, 1.26), respectively. Conclusions Simvastatin has no clinically important effect on sitagliptin pharmacokinetics. No dose adjustment for either sitagliptin or simvastatin is recommended when these drugs are coadministered.