title: Effect of multiple-dose dexloxiglumide on the pharmacokinetics of oral contraceptives in healthy women.
abstract: This study was undertaken to evaluate the effect of dexloxiglumide, a selective cholecystokinin receptor antagonist, on the pharmacokinetics of a combination oral contraceptive (OC). A single-blind, placebo-controlled, 2-period crossover study was conducted in 24 healthy young female subjects who received Ortho Tri-Cyclen containing ethinyl estradiol (EE, 0.035 mg) and norgestimate (NE, 0.180 mg/0.215 mg/0.250 mg per 7-day phase, respectively) for 5 days (days 17-21) concurrently with either 200 mg dexloxiglumide (3 times a day on days 17-20, followed by a single dose on day 21) or matching placebo during 2 consecutive 28-day OC dosing cycles. Plasma was sampled up to 24 hours for the determination of EE, NE, and 17-deactyl norgestimate (17-DNE, a rapidly formed pharmacologically active metabolite of NE). The geometric mean ratios (GMRs, dexloxiglumide/placebo) of the plasma concentration-time curve over 24 hours with corresponding 90% confidence intervals (CIs) for EE and 17-DNE were 1.21 (1.17-1.26) and 0.92 (0.89-0.95), respectively. The GMRs (90% CI) of C(max) for EE and 17-DNE were 1.15 (1.09-1.20) and 0.93 (0.90-0.96), respectively. Coadministration of OC and dexloxiglumide was well tolerated and safe. Comparable systemic exposure of EE and 17-DNE in the presence and absence of dexloxiglumide suggests that dexloxiglumide treatment is unlikely to interfere with the safety and efficacy of oral contraceptives based on the analysis of the resulting pharmacokinetic profile.
authors.affiliation: Department of Clinical Pharmacology and Drug Dynamics, Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ 07311, USA.
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
authors.forename: Abhijeet S
authors.initials: AS
authors.lastname: Jakate
authors.forename: Alpita
authors.initials: A
authors.lastname: Patel
authors.forename: Wattanaporn
authors.initials: W
authors.lastname: Abramowitz
authors.forename: Julie
authors.initials: J
authors.lastname: Wangsa
authors.forename: Stefano
authors.initials: S
authors.lastname: Persiani
authors.forename: Ram
authors.initials: R
authors.lastname: Kapil
mesh_terms: D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000031:analogs & derivatives / Q000097:blood; D008597:Menstrual Cycle; D008875:Middle Aged; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010091:Oximes; D010421:Pentanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors
chemical_list: D003280:Contraceptives, Oral, Synthetic; D004338:Drug Combinations; D010091:Oximes; D010421:Pentanoic Acids; D011949:Receptors, Cholecystokinin; C109079:norgestimate, ethinyl estradiol drug combination; D009644:Norgestrel; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; C103490:dexloxiglumide; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C449219:norelgestromin