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PIII‐64
Author(s) -
Wright D.,
Maes A.,
Yi B.,
Bergman A. J.,
Liu Q.,
Lasseter K. C.,
Gottesdiener K. M.,
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.2005.12.272
Subject(s) - sitagliptin , pharmacokinetics , pharmacodynamics , pharmacology , dipeptidyl peptidase 4 , medicine , dipeptidyl peptidase 4 inhibitor , warfarin , dipeptidyl peptidase , chemistry , endocrinology , diabetes mellitus , type 2 diabetes , enzyme , biochemistry , atrial fibrillation
BACKGROUND Sitagliptin is an orally active, potent and selective DPP‐IV inhibitor in Phase III trials for the treatment of type 2 diabetes. DPP‐IV inhibitors enhance levels of active GLP‐1 and other incretins, facilitating glucose‐dependent insulin secretion. METHODS 12 healthy young male and female volunteers received a single open‐label dose of 30 mg warfarin (Bristol‐Myers Squibb Company) on Day 5 during 11 days of once‐a‐day open‐label dosing with sitagliptin 200 mg, or a single open‐label dose of 30 mg warfarin on Day 1, in this randomized, multiple‐dose, open‐label, 2‐period, crossover study. RESULTS Sitagliptin was generally well tolerated. For S(−) and R(+) warfarin, no statistically significant differences in plasma AUC 0‐∞ were observed and slight reductions in C max were not considered clinically relevant. Prothrombin time (measured by INR) was not altered. (See Table)Least Squares Mean GMR (CI) Warfarin + MK‐0431 Warfarin Alone Warfarin + MK‐0431 / Warfarin AloneS(−) Warfarin AUC (0‐∞) (μg · hr/mL) 70.7 74.1 0.95 (0.90, 1.02) ‡ S(−) Warfarin C max (ng/mL) 1958 2198 0.89 (0.86, 0.92) ‡ R(+) Warfarin AUC (0‐∞) (μg · hr/mL) 102.6 103.3 0.99 (0.95, 1.03) ‡ R(+) Warfarin C max (ng/mL) 1917 2144 0.89 (0.86, 0.93) ‡ INR AUC (0–168hr) 260 257 1.01 (0.96, 1.06) ¶ INR max 2.27 2.10 1.08 (1.00, 1.17) ¶90% CI 95% CICONCLUSIONS Sitagliptin is well tolerated. Sitagliptin does not meaningfully alter the single dose pharmacokinetics of warfarin (either R or S enantiomers of warfarin) or the single dose pharmacodynamics of warfarin as assessed by prothrombin time INR. Co‐administration of sitagliptin and warfarin to healthy subjects is generally well tolerated and these data do not suggest that dosage adjustment for warfarin is necessary when co‐administered with sitagliptin. Clinical Pharmacology & Therapeutics (2005) 79 , P76–P76; doi: 10.1016/j.clpt.2005.12.272