EFFECT OF SIMVASTATIN ON THE PHARMACOKINETICS OF SITAGLIPTIN

Main Article Content

Michael Cerra
Wen-Lin Luo
Susie (Xiujiang) Li
Catherine Matthews
Edward A O'Neill
John A Wagner
S Aubrey Stoch
Matt S Anderson

Keywords

Type 2 diabetes, atherosclerosis, dipeptidyl peptidase-4, statin, HMG-CoA reductase, drug interactions

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-∞ andCmax 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.

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