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Title: Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women
Authors: Anna H. Tran
Brookie M. Best
Alice Stek
Jiajia Wang
Edmund V. Capparelli
Sandra K. Burchett
Regis Kreitchmann
Kittipong Rungruengthanakit
Kathleen George
Tim R. Cressey
Nahida Chakhtoura
Elizabeth Smith
David E. Shapiro
Mark Mirochnick
Shelley Buschur
Chivon Jackson
Mary Paul
Donna McGregor
Ram Yogev
Rohit Kalra
Claudia Florez
Patricia Bryan
Monica Stone
Andrew D. Hull
Mary Caffery
Stephen A. Spector
Joan Wilson
Julieta Giner
Margaret A. Donnelly
Ellen R. Cooper
Debra A. McLaud
Lisa F. Tucker
Jane Hitti
Amanda Robson-Nuss
Ann J. Melvin
Margaret A. Keller
Michael A. Bolaris
Judy Hayes
Françoise Kamer
La Shonda Spencer
James Homans
Torri Metz
Jenna Wallace
Alisa Katai
Mariam Aziz
Maureen McNichols
Julie Schmidt
Diane Wara
Kristinalisa Maka
Deborah Cohan
Audra Deveikis
Jagmohan Batra
Janielle Jackson Alvarez
Michele Carter
Jaime Deville
Carla Janzen
Jenny Gutierrez
Martha Cavallo
Murli Purswani
Katherine M. Knapp
Nina Sublette
Thomas Wride
Keywords: Medicine
Issue Date: 1-Jul-2016
Abstract: © Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved. 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) AUC0-24were 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) C24were 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. Cminwere 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). Cminwas below the protein binding-adjusted EC90concentration (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 EC90for rilpivirine.
ISSN: 10779450
Appears in Collections:CMUL: Journal Articles

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