TY - JOUR
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
N1 - Publisher Copyright:
© 2016 Mulligan, Schalkwijk, Best, Colbers, Wang, Capparelli, Moltó, Stek, Taylor, Smith, Hidalgo Tenorio, Chakhtoura, van Kasteren, Fletcher, Mirochnick, Burger and on behalf of the PANNA Network and the IMPAACT 1026s Study Teams.
PY - 2016/8/4
Y1 - 2016/8/4
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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UR - http://www.scopus.com/inward/citedby.url?scp=84988644183&partnerID=8YFLogxK
U2 - 10.3389/fphar.2016.00239
DO - 10.3389/fphar.2016.00239
M3 - Article
C2 - 27540363
AN - SCOPUS:84988644183
SN - 1663-9812
VL - 7
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
IS - AUG
M1 - 239
ER -