title: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, does not affect the pharmacokinetics of ethinyl estradiol or norethindrone in healthy female subjects.
abstract: Sitagliptin is a dipeptidyl peptidase-IV (DPP-4) inhibitor used for the treatment of patients with type 2 diabetes mellitus. This randomized, placebo-controlled, 2-period, crossover study evaluated the effect of sitagliptin on the pharmacokinetics of 17 α-ethinyl estradiol (EE(2)) and norethindrone (NET) in healthy female subjects who were receiving oral contraceptives for >3 months prior to enrollment. A total of 18 subjects with normal menstrual cycles received the oral contraceptive pill ORTHO-NOVUM(®) 7/7/7 on days 1 to 28 for 2 successive cycles, and on days 1 to 21 were randomly assigned to receive sitagliptin 200 mg/day (2 × 100 mg tablets) or placebo using a computer-generated allocation schedule. Blood samples for determination of plasma EE(2) and NET concentrations were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours postdose on day 20 or 21 of each treatment period. The GMRs (90% confidence interval [CI]) for the AUC(0-24 hr) of EE(2) and NET were 0.99 (0.93, 1.06) and 1.03 (0.97, 1.09), respectively, and for C(max) were 0.97 (0.86, 1.10) and 0.98 (0.89, 1.07), respectively. The coadministration of sitagliptin 200 mg/day with an oral contraceptive for 21 days did not lead to clinically meaningful alterations in the pharmacokinetics of EE(2) and NET.
authors.affiliation: Merck & Co, Inc, Rahway, New Jersey, USA. elizabeth_migoya@merck.com
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Migoya
authors.forename: Patrick
authors.initials: P
authors.lastname: Larson
authors.forename: Arthur
authors.initials: A
authors.lastname: Bergman
authors.forename: Jutta
authors.initials: J
authors.lastname: Miller
authors.forename: Amy O
authors.initials: AO
authors.lastname: Johnson-Levonas
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Lasseter
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
mesh_terms: D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000097:blood; D018592:Cross-Over Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000097:blood*; D004347:Drug Interactions / Q000502:physiology; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000097:blood*; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000008:administration & dosage* / Q000097:blood*; D011719:Pyrazines / Q000008:administration & dosage / Q000097:blood*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood*; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D004997:Ethinyl Estradiol; D009640:Norethindrone; D000068900:Sitagliptin Phosphate