- OBJECTIVE: Pharmacokinetic interactions exist between combined
oral contraceptives and protease inhibitors (PI). However, such
information is lacking for progestin-only oral contraception. We
sought to define the steady-state pharmacokinetic interaction between
norethindrone (NET) and PI in HIV-infected women.
METHODS AND DESIGN: We conducted an open-label, prospective,
nonrandomized trial to characterize the steady-state pharmacokinetics
of serum NET in HIV-infected women receiving PI compared
with a control group of HIV-infected women receiving other
noninteracting drugs. After 21 days of 0.35 mg of NET ingestion
once daily, serial serum samples were obtained at 0, 1, 2, 3, 4, 6, 8,
12, 24, 48, and 72 hours. The area under the curve between 0 and
72 hours after ingestion was calculated by trapezoidal approximation.
RESULTS: Thirty-five women were enrolled, 2 withdrew. Sixteen
women in the PI group and 17 controls completed the study. NET
half-life and maximum concentration were not significantly different
between the 2 groups. Minimum concentration of NET was significantly
higher in the PI group (P = 0.01). The ratio of the geometric
mean NET area under the curve in the PI group compared with controls
was 1.5 (90% confidence interval: 1.21 to 1.86). NET serum
concentrations were significantly higher in HIV-infected women taking
a PI compared with controls (P = 0.004).
CONCLUSIONS: Coadministration of PI inhibits NET metabolism as
shown by higher serum NET area under the curve levels, a surrogate
marker for therapeutic contraceptive efficacy. This study supports
the increased utilization of progestin-only pills in HIV-infected
women receiving certain PI regimens.
- Atrio, J., Stanczyk, F. Z., Neely, M., Cherala, G., Kovacs, A., & Mishell Jr, D. R. (2014). Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women. Journal of Acquired Immune Deficiency Syndromes, 65(1), 72-77. doi:10.1097/QAI.0b013e3182a9b3f1
|Funding Statement (additional comments about funding)
- Supported by the Society of Family Planning, Southern California Clinical, and
Translational Science Institute (The National Institutes of Health, National
Center for Research Resources, National Center for Advancing Translational
Sciences) (through grant UL1TR000130 for J.A.), and the National
Institutes of Health Grants (GM068968 and HD070886 for M.N.).