Effect of Multiple-Dose Dexloxiglumide on the Pharmacokinetics of Oral Contraceptives in Healthy Women

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 re...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2005-03, Vol.45 (3), p.329-336
Main Authors: Roy, Partha, Jakate, Abhijeet S., Patel, Alpita, Abramowitz, Wattanaporn, Wangsa, Julie, Persiani, Stefano, Kapil, Ram
Format: Article
Language:English
Subjects:
Adult
Contraceptives, Oral, Synthetic - pharmacokinetics
Cross-Over Studies
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - metabolism
Dexloxiglumide
Drug Interactions
Ethinyl Estradiol - blood
Ethinyl Estradiol - pharmacokinetics
Female
Humans
Levonorgestrel - analogs & derivatives
Levonorgestrel - blood
Menstrual Cycle
Middle Aged
Norgestrel - analogs & derivatives
Norgestrel - pharmacokinetics
oral contraceptives
Oximes
Pentanoic Acids - administration & dosage
Pentanoic Acids - pharmacology
pharmacokinetics
Receptors, Cholecystokinin - antagonists & inhibitors
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Summary: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 Cmax 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.
ISSN:0091-2700
1552-4604
DOI:10.1177/0091270004272732