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

Br J Clin Pharmacol. 2011 Apr;71(4):616-20. doi: 10.1111/j.1365-2125.2010.03885.x.


Aims: 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)].

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Contraceptives, Oral, Synthetic / pharmacokinetics*
  • Drug Interactions
  • Estradiol / blood
  • Estradiol / pharmacokinetics*
  • Estrogens / pharmacokinetics*
  • Female
  • Humans
  • Middle Aged
  • Norgestrel / analogs & derivatives*
  • Norgestrel / blood
  • Norgestrel / pharmacokinetics
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / pharmacokinetics
  • Pyrrolidinones / pharmacokinetics*
  • Raltegravir Potassium
  • Statistics as Topic
  • Young Adult


  • Contraceptives, Oral, Synthetic
  • Estrogens
  • HIV-1 integrase (147-175)
  • Peptide Fragments
  • Pyrrolidinones
  • Norgestrel
  • Raltegravir Potassium
  • Estradiol
  • norgestimate