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Front Pharmacol. 2016 Aug 4;7:239. doi: 10.3389/fphar.2016.00239. eCollection 2016.

Etravirine Pharmacokinetics in HIV-Infected Pregnant Women.

Author information

1
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
2
Department of Pharmacy, Radboud University Medical Center Nijmegen, Netherlands.
3
Center for Biostatistics in AIDS Research, Harvard School of Public Health Boston, MA, USA.
4
Fundació Lluita contra la Sida, Hospital Universitari Germans Trias I Pujol Badalona, Spain.
5
Maternal Child and Adolescent/Adult Center, University of Southern California School of Medicine Los Angeles, CA, USA.
6
Imperial College Healthcare National Health Service Trust London, UK.
7
Maternal, Adolescent, and Pediatric Research Branch, National Institute of Allergy and Infectious Diseases Bethesda, MD, USA.
8
Hospital Universitario Virgen de las Nieves Granada Granada, Spain.
9
Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development Bethesda, MD, USA.
10
Department of Internal Medicine, St. Elisabeth Hospital Tilburg, Netherlands.
11
Antiviral Pharmacology Laboratory, College of Pharmacy, University of Nebraska Medical Center Omaha, NE, USA.
12
Department of Pediatrics, Boston University School of Medicine Boston, MA, USA.

Abstract

BACKGROUND:

The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women.

METHODS:

IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL).

RESULTS:

Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred.

CONCLUSION:

Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available.

CLINICAL TRIAL REGISTRATION:

The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929.

KEYWORDS:

HIV; etravirine; perinatal transmission; pharmacokinetics; pregnancy

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