The effects of simvastatin on the pharmacokinectics of sitagliptin.
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.
Merck Sharp & Dohme Corp., Whitehouse Station, NJ, UDA.
Michael
M
Cerra
Wen-Lin
WL
Luo
Susie Xiujiang
SX
Li
Catherine
C
Matthews
Edward A
EA
O'Neill
John A
JA
Wagner
S Aubrey
SA
Stoch
Matt S
MS
Anderson
D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D054873:Dipeptidyl-Peptidase IV Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011719:Pyrazines; D014230:Triazoles; D019821:Simvastatin; D000068900:Sitagliptin Phosphate