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Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women

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-infe...

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Autores principales: Atrio, Jessica, Stanczyk, Frank Z., Neely, Michael, Cherala, Ganesh, Kovacs, Andrea, Mishell, Daniel R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JAIDS Journal of Acquired Immune Deficiency Syndromes 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946363/
https://www.ncbi.nlm.nih.gov/pubmed/24025339
http://dx.doi.org/10.1097/QAI.0b013e3182a9b3f1
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author Atrio, Jessica
Stanczyk, Frank Z.
Neely, Michael
Cherala, Ganesh
Kovacs, Andrea
Mishell, Daniel R.
author_facet Atrio, Jessica
Stanczyk, Frank Z.
Neely, Michael
Cherala, Ganesh
Kovacs, Andrea
Mishell, Daniel R.
author_sort Atrio, Jessica
collection PubMed
description 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.
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spelling pubmed-39463632014-04-15 Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women Atrio, Jessica Stanczyk, Frank Z. Neely, Michael Cherala, Ganesh Kovacs, Andrea Mishell, Daniel R. J Acquir Immune Defic Syndr Clinical Science 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. JAIDS Journal of Acquired Immune Deficiency Syndromes 2014-01-01 2014-01-01 /pmc/articles/PMC3946363/ /pubmed/24025339 http://dx.doi.org/10.1097/QAI.0b013e3182a9b3f1 Text en Copyright © 2013 by Lippincott Williams & Wilkins http://creativecommons.org/licenses/by-nc-nd/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Clinical Science
Atrio, Jessica
Stanczyk, Frank Z.
Neely, Michael
Cherala, Ganesh
Kovacs, Andrea
Mishell, Daniel R.
Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women
title Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women
title_full Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women
title_fullStr Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women
title_full_unstemmed Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women
title_short Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women
title_sort effect of protease inhibitors on steady-state pharmacokinetics of oral norethindrone contraception in hiv-infected women
topic Clinical Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946363/
https://www.ncbi.nlm.nih.gov/pubmed/24025339
http://dx.doi.org/10.1097/QAI.0b013e3182a9b3f1
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