Premium
Multiple‐Dose Administration of Sitagliptin, a Dipeptidyl Peptidase‐4 Inhibitor, Does Not Alter the Single‐Dose Pharmacokinetics of Rosiglitazone in Healthy Subjects
Author(s) -
Mistry Goutam C.,
Bergman Arthur J.,
Luo WenLin,
Cilissen Caroline,
Haazen Wouter,
Davies Michael J.,
Gottesdiener Keith M.,
Wagner John A.,
Herman Gary A.
Publication year - 2007
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 - 10.1177/0091270006297007
Subject(s) - sitagliptin , rosiglitazone , dipeptidyl peptidase 4 inhibitor , pharmacokinetics , medicine , pharmacology , cmax , dipeptidyl peptidase 4 , sitagliptin phosphate , incretin , crossover study , endocrinology , type 2 diabetes , diabetes mellitus , insulin , placebo , alternative medicine , pathology
Sitagliptin, a dipeptidyl peptidase‐4 inhibitor, is an incretin enhancer that is approved for the treatment of type 2 diabetes. Sitagliptin is mainly renally eliminated and not a potent inhibitor of CYP450 enzymes in vitro. Rosiglitazone, a thiazolidenedione, is an insulin sensitizer and mainly metabolized by CYP2C8. Since both agents may potentially be coadministered, the purpose of this study was to examine the effects of sitagliptin on rosiglitazone pharmacokinetics. In this open‐label, randomized, 2‐period, crossover study, 12 healthy normoglycemic subjects, 21 to 44 years, received single 4‐mg doses of rosiglitazone alone in one period and coadministered with sitagliptin on day 5 following a multiple‐dose regimen for sitagliptin (200 mg once daily × 5 days) in the other period. The geometric mean ratios and 90% confidence intervals ([rosiglitazone + sitagliptin]/rosiglitazone) for rosiglitazone AUC 0‐∞ and C max were 0.98 (0.93, 1.02) and 0.99 (0.88, 1.12), respectively. In conclusion, sitagliptin did not alter the pharmacokinetics of rosiglitazone in healthy subjects.