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Multiple Doses of Sitagliptin, a Selective DPP‐4 Inhibitor, Do Not Meaningfully Alter Pharmacokinetics and Pharmacodynamics of Warfarin
Author(s) -
Wright D. Hamish,
Herman Gary A.,
Maes Andrea,
Liu Qi,
JohnsonLevonas Amy O.,
Wagner John A.
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009341653
Subject(s) - sitagliptin , warfarin , pharmacodynamics , pharmacokinetics , pharmacology , crossover study , medicine , sitagliptin phosphate , drug interaction , diabetes mellitus , type 2 diabetes , endocrinology , placebo , atrial fibrillation , alternative medicine , pathology
Sitagliptin is an orally active, highly selective dipeptidyl peptidase IV (DPP‐4) inhibitor for treatment of type 2 diabetes mellitus. This randomized, open‐label, 2‐part, 2‐period crossover study assessed pharmacokinetics/pharmacodynamics of warfarin in the presence/absence of multiple‐dose sitagliptin. Twelve participants received treatments A and B separated by >7‐day washout: treatment A involved coadministration of sitagliptin 200 mg/d for 11 days (days 1–11) and warfarin 30 mg on day 5, and treatment B involved warfarin 30 mg alone on day 1. R(+) warfarin, S(−) warfarin, and international normalized ratio (INR) were assayed predose and up to 168 hours postdose. The geometric mean ratios (GMRs; warfarin + sitagliptin/warfarin alone) (90% confidence intervals [CIs]) were 0.99 (0.95, 1.03) and 0.95 (0.90, 1.02) for the AUC 0‐∞ of R(+) and S(−) warfarin, respectively. GMRs (warfarin + sitagliptin/warfarin alone) (90% CIs) were 0.89 (0.86, 0.93) and 0.89 (0.86, 0.92) for the C max of R(+) and S(−) warfarin, respectively. INR AUC 0–168 h and INR max GMRs were 1.01 (0.96, 1.06) and 1.08 (1.00, 1.17), respectively. Coadministration of sitagliptin and warfarin was generally well tolerated. Pharmacokinetics (AUC for R(+) and S(−) warfarin) and pharmacodynamics (INR of R(+) or S(−) warfarin) were not meaningfully altered following coadministration of multiple‐dose sitagliptin and single‐dose warfarin, indicating that no dosage adjustment for warfarin is necessary when coadministered with sitagliptin.