Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women

Merck Research Labs, Merck & Co., Inc., Whitehouse Station, NJ 07065-0900, USA.
British Journal of Clinical Pharmacology (Impact Factor: 3.88). 04/2011; 71(4):616-20. DOI: 10.1111/j.1365-2125.2010.03885.x
Source: PubMed


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.

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Available from: William D Hanley, Dec 16, 2013
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    • "A randomized two-arm crossover study investigating interactions between raltegravir and a triphasic COC containing EE/norgestimate found no difference in EE PK parameters between the two groups. There were small decreases in the Cmin⁡ and AUC of norelgestromin, the active metabolite of norgestimate, but these were not felt to be clinically significant [23]. "
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    British Journal of Clinical Pharmacology 04/2011; 71(4):485-6. DOI:10.1111/j.1365-2125.2011.03951.x · 3.88 Impact Factor
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