Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women
- 11 March 2011
- journal article
- research article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 71 (4), 616-620
- https://doi.org/10.1111/j.1365-2125.2010.03885.x
Abstract
Oral contraceptives such as norgestimate-ethinyl estradiol (Ortho Tri-Cyclen®) are commonly prescribed in the HIV-infected patient population. A placebo-controlled, randomized, two-period crossover study in healthy HIV-seronegative subjects was conducted to assess the effect of raltegravir on the pharmacokinetics of the estrogen and progestin components of norgestimate-ethinyl estradiol [ethinyl estradiol (EE) and norelgestromin (NGMN), an active metabolite of norgestimate (NGT)]. In each of two periods, nineteen healthy women established on norgestimate-ethinyl estradiol contraception (21 days of active contraception; 7 days of placebo) received either 400 mg raltegravir or matching placebo twice daily on days 1-21. Pharmacokinetics were analysed on day 21 of each period. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the EE component of norgestimate-ethinyl estradiol when co-administrated with raltegravir relative to EE alone was 0.98 (0.93-1.04) for the area under the concentration-time curve from 0 to 24 h (AUC(0-24 h) ) and 1.06 (0.98-1.14) for the maximum concentration of drug in the plasma (C(max) ); the GMR (90% CI) for the NGMN component of norgestimate-ethinyl estradiol when co-administered with raltegravir relative to NGMN alone was 1.14 (1.08-1.21) for AUC(0-24 h) and 1.29 (1.23-1.37) for C(max) . There were no discontinuations due to a study drug-related adverse experience, nor any serious clinical or laboratory adverse experience. Raltegravir has no clinically important effect on EE or NGMN pharmacokinetics. Co-administration of raltegravir and an oral contraceptive containing EE and NGT was generally well tolerated; no dose adjustment is required for oral contraceptives containing EE and NGT when co-administered with raltegravir.This publication has 8 references indexed in Scilit:
- Oral Contraceptive ToleranceObstetrics & Gynecology, 2007
- Serum distribution of the major metabolites of norgestimate in relation to its pharmacological propertiesContraception, 2003
- Contraception for women in selected circumstancesObstetrics & Gynecology, 2002
- Pharmacokinetics of a contraceptive patch (Evra™/Ortho Evra™) containing norelgestromin and ethinyloestradiol at four application sitesBritish Journal of Clinical Pharmacology, 2002
- Determination of norgestimate and its metabolites in human serum using high-performance liquid chromatography with tandem mass spectrometric detectionJournal of Chromatography B: Biomedical Sciences and Applications, 1999
- The pharmacokinetics and metabolism of ethinyl estradiol and its three sulfates in the baboonAmerican Journal of Obstetrics and Gynecology, 1983
- First-Pass Metabolism of Ethinyl Estradiol in Dogs and RatsJournal of Pharmaceutical Sciences, 1981