title: Multiple-dose administration of sitagliptin, a dipeptidyl peptidase-4 inhibitor, does not alter the single-dose pharmacokinetics of rosiglitazone in healthy subjects.
abstract: 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 x 5 days) in the other period. The geometric mean ratios and 90% confidence intervals ([rosiglitazone + sitagliptin]/rosiglitazone) for rosiglitazone AUC(0-infinity) and Cmax 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.
authors.affiliation: Merck Research Laboratories, Mail Code RY34-A536, PO Box 2000, Rahway, NJ 07065-0900, USA.
authors.forename: Goutam C
authors.initials: GC
authors.lastname: Mistry
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Bergman
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Luo
authors.forename: Caroline
authors.initials: C
authors.lastname: Cilissen
authors.forename: Wouter
authors.initials: W
authors.lastname: Haazen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Keith M
authors.initials: KM
authors.lastname: Gottesdiener
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Gary A
authors.initials: GA
authors.lastname: Herman
mesh_terms: D058892:Adenosine Deaminase Inhibitors; D000328:Adult; D018592:Cross-Over Studies; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004347:Drug Interactions; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011719:Pyrazines / Q000008:administration & dosage*; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000097:blood / Q000493:pharmacokinetics*; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D058892:Adenosine Deaminase Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins; D007004:Hypoglycemic Agents; D011719:Pyrazines; D045162:Thiazolidinediones; D014230:Triazoles; D000077154:Rosiglitazone; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate