title: Sitagliptin, an dipeptidyl peptidase-4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects.
abstract: OBJECTIVE
  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 an inhibitor of CYP450 enzymes in vitro. Glyburide, a sulphonylurea, is an insulin sensitizer and mainly metabolized by CYP2C9. Since both agents may potentially be co-administered, the purpose of this study was to examine the effects of sitagliptin on glyburide pharmacokinetics.
  
  
  METHODS
  In this open-label, randomized, two-period crossover study, eight healthy normoglycaemic subjects, 22-44 years old, received single 1.25-mg doses of glyburide alone in one period and co-administered with sitagliptin on day 5 following a multiple-dose regimen for sitagliptin (200-mg q.d. x 6 days) in the other period.
  
  
  RESULTS
  The geometric mean ratios and 90% confidence intervals [(glyburide + sitagliptin)/glyburide] for AUC(0-infinity) and C(max) were 1.09 (0.96, 1.24) and 1.01 (0.84, 1.23), respectively.
  
  
  CONCLUSIONS
  Sitagliptin does not alter the pharmacokinetics of glyburide in healthy subjects.
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: Goutam C
authors.initials: GC
authors.lastname: Mistry
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Bergman
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: David
authors.initials: D
authors.lastname: Hreniuk
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Zinny
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
authors.forename: Marcella
authors.initials: M
authors.lastname: Ruddy
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005905:Glyburide / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D005905:Glyburide; D000068900:Sitagliptin Phosphate