Etravirine pharmacokinetics in HIV-infected pregnant women

on behalf of the PANNA Network and the IMPAACT 1026s Study Teams

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article number239
JournalFrontiers in Pharmacology
Volume7
Issue numberAUG
DOIs
StatePublished - Aug 4 2016

Fingerprint

etravirine
Pregnant Women
Pharmacokinetics
HIV
Postpartum Period
Pregnancy Trimesters
Safety
Third Pregnancy Trimester
Fetal Blood
Liquid Chromatography
Limit of Detection

Keywords

  • Etravirine
  • HIV
  • Perinatal transmission
  • Pharmacokinetics
  • Pregnancy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

on behalf of the PANNA Network and the IMPAACT 1026s Study Teams (2016). Etravirine pharmacokinetics in HIV-infected pregnant women. Frontiers in Pharmacology, 7(AUG), [239]. https://doi.org/10.3389/fphar.2016.00239

Etravirine pharmacokinetics in HIV-infected pregnant women. / on behalf of the PANNA Network and the IMPAACT 1026s Study Teams.

In: Frontiers in Pharmacology, Vol. 7, No. AUG, 239, 04.08.2016.

Research output: Contribution to journalArticle

on behalf of the PANNA Network and the IMPAACT 1026s Study Teams 2016, 'Etravirine pharmacokinetics in HIV-infected pregnant women', Frontiers in Pharmacology, vol. 7, no. AUG, 239. https://doi.org/10.3389/fphar.2016.00239
on behalf of the PANNA Network and the IMPAACT 1026s Study Teams. Etravirine pharmacokinetics in HIV-infected pregnant women. Frontiers in Pharmacology. 2016 Aug 4;7(AUG). 239. https://doi.org/10.3389/fphar.2016.00239
on behalf of the PANNA Network and the IMPAACT 1026s Study Teams. / Etravirine pharmacokinetics in HIV-infected pregnant women. In: Frontiers in Pharmacology. 2016 ; Vol. 7, No. AUG.
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T1 - Etravirine pharmacokinetics in HIV-infected pregnant women

AU - on behalf of the PANNA Network and the IMPAACT 1026s Study Teams

AU - Mulligan, Nikki

AU - Schalkwijk, Stein

AU - Best, Brookie M.

AU - Colbers, Angela

AU - Wang, Jiajia

AU - Capparelli, Edmund V.

AU - Moltó, José

AU - Stek, Alice M.

AU - Taylor, Graham

AU - Smith, Elizabeth

AU - Tenorio, Carmen Hidalgo

AU - Chakhtoura, Nahida

AU - van Kasteren, Marjo

AU - Fletcher, Courtney V

AU - Mirochnick, Mark

AU - Burger, David

AU - Antinori, Andrea

AU - Ende, Ineke van der

AU - Faetkenheuer, Gerd

AU - Giaquinto, Carlo

AU - Gilleece, Yvonne

AU - Gingelmaier, Andrea

AU - Haberl, Annette

AU - Hawkins, David

AU - Ivanovic, Jelena

AU - Kabeya, Kabamba

AU - Lambert, John

AU - Lyons, Fyona

AU - Nellen, Jeannine

AU - Nicastri, Emanuelle

AU - Rockstroh, Jürgen

AU - Schwarze-Zander, Caroline

AU - Ruiter, Annemiek de

AU - Sadiq, Tariq

AU - Ven, André van der

AU - Weizsäcker, Katharina

AU - Wood, Chris

AU - Wyen, Christoph

PY - 2016/8/4

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N2 - 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.

AB - 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.

KW - Etravirine

KW - HIV

KW - Perinatal transmission

KW - Pharmacokinetics

KW - Pregnancy

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DO - 10.3389/fphar.2016.00239

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