Premium
PII‐46
Author(s) -
Bergman A. J.,
Cote J.,
Maes A.,
Zhao J.,
Roadcap B.,
Sun L.,
Valesky R.,
Yang A.,
Keymeulen B.,
Wagner J. A.,
Herman G. A.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.171
Subject(s) - simvastatin , sitagliptin , cmax , pharmacokinetics , pharmacology , dipeptidyl peptidase 4 inhibitor , medicine , atorvastatin , chemistry , endocrinology , type 2 diabetes , metformin , diabetes mellitus , insulin
BACKGROUND/AIMS MK‐0431 (sitagliptin) is a selective DPP‐IV inhibitor in Phase III development for the treatment of type 2 diabetes. Since sitagliptin is expected to be commonly co‐administered with statins, the effect of sitagliptin on the pharmacokinetics (PK) of simvastatin, a CYP3A4 substrate, was evaluated. METHODS Twelve healthy subjects were randomized to 2 treatment periods: (A) a single oral dose of simvastatin 20 mg and (B) daily oral doses of 200 mg sitagliptin on Days 1 through 5 and a single oral dose of simvastatin 20 mg on Day 5. Plasma was collected for 24 hours following each simvasatin dose to determine the PK of active HMG‐CoA reductase inhibitors (represents all active inhibitors in plasma; primary analyte), total HMG‐CoA reductase inhibitors, simvastatin, and simvastatin acid. RESULTS Active inhibitor geometric mean ratio (simvastatin+sitagliptin/simvastatin) and the 90% CI for AUC 0‐last and C max were 1.06 (0.88, 1.26) and 0.94 (0.66, 1.34), respectively, with no meaningful difference in T max between treatments (median 1.8 hours for both treatments). Additionally, there were no clinically or statistically meaningful differences in AUC 0‐last , C max or T max between treatments for the other three analytes evaluated (total inhibitors, simvastatin and simvastatin acid). Sitagliptin and simvastatin were well tolerated. CONCLUSIONS Multiple oral doses of sitagliptin do not meaningfully alter the pharmacokinetics of simvastatin. Clinical Pharmacology & Therapeutics (2005) 79 , P48–P48; doi: 10.1016/j.clpt.2005.12.171