TY - JOUR
T1 - Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women
AU - for the IMPAACT P1026s Protocol Team
AU - Tran, Anna H.
AU - Best, Brookie M.
AU - Stek, Alice
AU - Wang, Jiajia
AU - Capparelli, Edmund V.
AU - Burchett, Sandra K.
AU - Kreitchmann, Regis
AU - Rungruengthanakit, Kittipong
AU - George, Kathleen
AU - Cressey, Tim R.
AU - Chakhtoura, Nahida
AU - Smith, Elizabeth
AU - Shapiro, David E.
AU - Mirochnick, Mark
AU - Buschur, Shelley
AU - Jackson, Chivon
AU - Paul, Mary
AU - McGregor, Donna
AU - Yogev, Ram
AU - Kalra, Rohit
AU - Florez, Claudia
AU - Bryan, Patricia
AU - Stone, Monica
AU - Hull, Andrew D.
AU - Caffery, Mary
AU - Spector, Stephen A.
AU - Wilson, Joan
AU - Giner, Julieta
AU - Donnelly, Margaret A.
AU - Cooper, Ellen R.
AU - McLaud, Debra A.
AU - Tucker, Lisa F.
AU - Hitti, Jane
AU - Robson-Nuss, Amanda
AU - Melvin, Ann J.
AU - Keller, Margaret A.
AU - Bolaris, Michael A.
AU - Hayes, Judy
AU - Kamer, Françoise
AU - Spencer, La Shonda
AU - Homans, James
AU - Metz, Torri
AU - Wallace, Jenna
AU - Katai, Alisa
AU - Aziz, Mariam
AU - McNichols, Maureen
AU - Schmidt, Julie
AU - Wara, Diane
AU - Maka, Kristinalisa
AU - Cohan, Deborah
N1 - Funding Information:
Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). A.T. was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development award number T35HD064385. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Background: Rilpivirine pharmacokinetics is defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4. The impact of pregnancy on rilpivirine pharmacokinetics is largely unknown. Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is a multicenter, nonblinded, prospective study evaluating antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving rilpivirine 25 mg once daily as part of their combination antiretrovirals for clinical care. Thirty-two women were enrolled in this study. Intensive pharmacokinetic sampling was performed at steady state during the second trimester, the third trimester, and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma rilpivirine concentration was measured using liquid chromatography-mass spectrometry; lower limit of quantitation was 10 ng/mL. Results: Median (range) AUC0-24 were 1969 (867-4987, n 15), 1669 (556-4312, n 28), and 2387 (188-6736, n 28) ng·h/mL in the second trimester, the third trimester, and postpartum, respectively (P < 0.05 for either trimester vs postpartum). Median (range) C24 were 63 (37-225, n 17), 56 (<10-181, n 30), and 81 (<10-299, n 28) ng/mL (P < 0.05 for either trimester vs postpartum). High variability in pharmacokinetic parameters was observed between subjects. Median (range) cord blood/maternal concentration ratio was 0.55 (0.3-0.8, n 21). Delivery HIV-1 RNA was ≤50 copies per milliliter in 70% and ≤400 copies per milliliter in 90% of women. Cmin were significantly lower at 15 visits with detectable HIV-1 RNA compared with 61 visits with undetectable HIV-1 RNA, 29 (<10-93) vs 63 (15-200) ng/mL (P 0.0001). Cmin was below the protein binding-adjusted EC90 concentration (12.2 ng/mL) at 4 visits in 3 of 31 women (10%). Conclusions: Rilpivirine exposure is lower during pregnancy compared with postpartum and highly variable. Ninety percent of women had minimum concentrations above the protein binding-adjusted EC90 for rilpivirine.
AB - Background: Rilpivirine pharmacokinetics is defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4. The impact of pregnancy on rilpivirine pharmacokinetics is largely unknown. Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is a multicenter, nonblinded, prospective study evaluating antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving rilpivirine 25 mg once daily as part of their combination antiretrovirals for clinical care. Thirty-two women were enrolled in this study. Intensive pharmacokinetic sampling was performed at steady state during the second trimester, the third trimester, and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma rilpivirine concentration was measured using liquid chromatography-mass spectrometry; lower limit of quantitation was 10 ng/mL. Results: Median (range) AUC0-24 were 1969 (867-4987, n 15), 1669 (556-4312, n 28), and 2387 (188-6736, n 28) ng·h/mL in the second trimester, the third trimester, and postpartum, respectively (P < 0.05 for either trimester vs postpartum). Median (range) C24 were 63 (37-225, n 17), 56 (<10-181, n 30), and 81 (<10-299, n 28) ng/mL (P < 0.05 for either trimester vs postpartum). High variability in pharmacokinetic parameters was observed between subjects. Median (range) cord blood/maternal concentration ratio was 0.55 (0.3-0.8, n 21). Delivery HIV-1 RNA was ≤50 copies per milliliter in 70% and ≤400 copies per milliliter in 90% of women. Cmin were significantly lower at 15 visits with detectable HIV-1 RNA compared with 61 visits with undetectable HIV-1 RNA, 29 (<10-93) vs 63 (15-200) ng/mL (P 0.0001). Cmin was below the protein binding-adjusted EC90 concentration (12.2 ng/mL) at 4 visits in 3 of 31 women (10%). Conclusions: Rilpivirine exposure is lower during pregnancy compared with postpartum and highly variable. Ninety percent of women had minimum concentrations above the protein binding-adjusted EC90 for rilpivirine.
KW - HIV
KW - pharmacokinetics
KW - pregnancy
KW - rilpivirine
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U2 - 10.1097/QAI.0000000000000968
DO - 10.1097/QAI.0000000000000968
M3 - Article
C2 - 26918544
AN - SCOPUS:84959196606
VL - 72
SP - 289
EP - 296
JO - Journal of acquired immune deficiency syndromes (1999)
JF - Journal of acquired immune deficiency syndromes (1999)
SN - 1525-4135
IS - 3
ER -