We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pharmacokinetic interaction between bosentan and the oral contraceptives norethisterone and ethinyl estradiol.
- Authors
van Giersbergen, P. L. M.; Halabi, A.; Dingemanse, J.
- Abstract
Objective: Bosentan has been shown in vitro and in vivo to induce the cytochrome P450 enzymes CYP2C9 and CYP3-A4. The present study was conducted to investigate the effect of bosentan on the pharmacokinetics of a combined oral contraceptive. Subjects and methods: In a randomized, 2-way cross over study, 20 healthy fe male subjects received Treatments A and B. Treatment A consisted of a single dose of Ortho-Novum containing 1 mg norethisterone (norethindrone) and 35 mg ethinyl estradiol. Treatment B consisted of bosentan, 125 mg b.i.d. for 7 days plus concomitant norethisterone and ethinyl estradiol on Day 7. Plasma concentrations of norethisterone and ethinyl estradiol were measured on days of oral contraceptive administration. Results: In the absence of bosentan, the pharmacokinetics of norethisterone and ethinyl estradiol were characterized by C max and AUC0-∞ values (95% CI) of 9.8 (8.1, 11.9) ng/ml and 72.9 (57.0, 93.1) ng × h/ml, and 53.0 (47.0, 59.9) pg/ml and 758 (655, 878) pg × h/ml, respectively. Concomitant bosentan did not affect the Cmax but significantly decreased the AUC of norethisterone and ethinyl estradiol by 13.7% (-23.5, -2.6) and 31.0% (-40.5, -20.2), respectively. The maximum decrease in AUC of norethisterone and ethinyl estradiol in an individual subject was 56% and 66%, respectively. Conclusions: Bosentan decreases the AUC of norethisterone and ethinyl estradiol in healthy female subjects. In patients treated with bosentan, reduced efficacy of hormonal contraceptives should be considered.
- Publication
International Journal of Clinical Pharmacology & Therapeutics, 2006, Vol 44, Issue 3, p113
- ISSN
0946-1965
- Publication type
Academic Journal
- DOI
10.5414/CPP44113