Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women

for the IMPAACT P1026s Protocol Team

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume72
Issue number3
DOIs
StatePublished - Jul 1 2016

Fingerprint

Rilpivirine
Pregnant Women
Pharmacokinetics
HIV
Postpartum Period
Protein Binding
HIV-1
Cytochrome P-450 CYP3A
Mothers
Third Pregnancy Trimester
Second Pregnancy Trimester
RNA
Fetal Blood
Pregnancy
Liquid Chromatography
Cardiac Output

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women. / for the IMPAACT P1026s Protocol Team.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 72, No. 3, 01.07.2016, p. 289-296.

Research output: Contribution to journalArticle

for the IMPAACT P1026s Protocol Team. / Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women. In: Journal of Acquired Immune Deficiency Syndromes. 2016 ; Vol. 72, No. 3. pp. 289-296.
@article{28b388486b4940a5b043503072b5da8e,
title = "Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women",
abstract = "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.",
author = "{for the IMPAACT P1026s Protocol Team} and Tran, {Anna H.} and Best, {Brookie M.} and Alice Stek and Jiajia Wang and Capparelli, {Edmund V.} and Burchett, {Sandra K.} and Regis Kreitchmann and Kittipong Rungruengthanakit and Kathleen George and Cressey, {Tim R.} and Nahida Chakhtoura and Elizabeth Smith and Shapiro, {David E.} and Mark Mirochnick and Shelley Buschur and Chivon Jackson and Mary Paul and Donna McGregor and Ram Yogev and Rohit Kalra and Claudia Florez and Patricia Bryan and Monica Stone and Hull, {Andrew D.} and Mary Caffery and Spector, {Stephen A.} and Joan Wilson and Julieta Giner and Donnelly, {Margaret A.} and Cooper, {Ellen R.} and McLaud, {Debra A.} and Tucker, {Lisa F.} and Jane Hitti and Amanda Robson-Nuss and Melvin, {Ann J.} and Keller, {Margaret A.} and Bolaris, {Michael A.} and Judy Hayes and Fran{\cc}oise Kamer and Spencer, {La Shonda} and James Homans and Torri Metz and Jenna Wallace and Alisa Katai and Mariam Aziz and Maureen McNichols and Julie Schmidt and Diane Wara and Kristinalisa Maka and Nina Sublette",
year = "2016",
month = "7",
day = "1",
doi = "10.1097/QAI.0000000000000968",
language = "English (US)",
volume = "72",
pages = "289--296",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

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 - Sublette, Nina

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.

UR - http://www.scopus.com/inward/record.url?scp=84959196606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959196606&partnerID=8YFLogxK

U2 - 10.1097/QAI.0000000000000968

DO - 10.1097/QAI.0000000000000968

M3 - Article

VL - 72

SP - 289

EP - 296

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 3

ER -