The effects of simvastatin on the pharmacokinectics of sitagliptin

J Popul Ther Clin Pharmacol. 2012;19(3):e356-60. Epub 2012 Oct 11.

Abstract

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 AUC0-∞ and Cmax 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Cross-Over Studies
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics*
  • Drug Interactions
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Middle Aged
  • Pyrazines / administration & dosage
  • Pyrazines / pharmacokinetics*
  • Simvastatin / administration & dosage
  • Simvastatin / pharmacology*
  • Sitagliptin Phosphate
  • Triazoles / administration & dosage
  • Triazoles / pharmacokinetics*
  • Young Adult

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrazines
  • Triazoles
  • Simvastatin
  • Sitagliptin Phosphate