Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum

Background: The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown. Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort...

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Main Authors: Cressey T., Stek A., Capparelli E., Bowonwatanuwong C., Prommas S., Sirivatanapa P., Yuthavisuthi P., Neungton C., Huo Y., Smith E., Best B., Mirochnick M.
Format: Journal
Published: 2017
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84859758788&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/42883
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spelling th-cmuir.6653943832-428832017-09-28T06:41:43Z Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum Cressey T. Stek A. Capparelli E. Bowonwatanuwong C. Prommas S. Sirivatanapa P. Yuthavisuthi P. Neungton C. Huo Y. Smith E. Best B. Mirochnick M. Background: The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown. Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg EFV once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6-12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile EFV area under the curve (AUC) in nonpregnant historical controls (40.0 mcghr ?1 mL ?1 ) and a trough concentration of 1 mcg/mL. Results: Twenty-five women were enrolled during the third trimester: median (range) age was 29.3 (18.9-42.9) years, weight 69.0 (40-130) kg, and gestational age 32.9 (30.1-38.7) weeks. Median (range) EFV AUC 0-24 , C max , and C 24 hours were 55.4 mcghr ?1 mL ?1 (13.5-220.3), 5.4 mcg/mL (1.9-12.2), and 1.6 mcg/mL (0.23-8.13), respectively. EFV AUC and Cmax did not differ during pregnancy and postpartum but C 24 hours was lower during the third trimester (1.6 vs. 2.1 mcg/mL, P = 0.01). During the third trimester, 5 of 25 (20%) women had an EFV AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. EFV cord blood/maternal concentration ratio was 0.49 (0.37-0.74). All women had a HIV-1 RNA viral load less than 400 copies per milliliter at delivery and 19 (76%) had a viral load below 50 copies per milliliter. One child was perinatally HIV infected. Three women were exposed to EFV throughout the first 6 weeks of pregnancy. EFV was well tolerated, and among the 25 infants, no congenital anomalies or newborn complications were reported. Conclusions: Changes in EFV pharmacokinetics during pregnancy compared with postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy. Copyright © 2012 by Lippincott Williams & Wilkins. 2017-09-28T06:41:43Z 2017-09-28T06:41:43Z 2012-03-01 Journal 15254135 2-s2.0-84859758788 10.1097/QAI.0b013e31823ff052 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84859758788&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/42883
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description Background: The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown. Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg EFV once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6-12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile EFV area under the curve (AUC) in nonpregnant historical controls (40.0 mcghr ?1 mL ?1 ) and a trough concentration of 1 mcg/mL. Results: Twenty-five women were enrolled during the third trimester: median (range) age was 29.3 (18.9-42.9) years, weight 69.0 (40-130) kg, and gestational age 32.9 (30.1-38.7) weeks. Median (range) EFV AUC 0-24 , C max , and C 24 hours were 55.4 mcghr ?1 mL ?1 (13.5-220.3), 5.4 mcg/mL (1.9-12.2), and 1.6 mcg/mL (0.23-8.13), respectively. EFV AUC and Cmax did not differ during pregnancy and postpartum but C 24 hours was lower during the third trimester (1.6 vs. 2.1 mcg/mL, P = 0.01). During the third trimester, 5 of 25 (20%) women had an EFV AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. EFV cord blood/maternal concentration ratio was 0.49 (0.37-0.74). All women had a HIV-1 RNA viral load less than 400 copies per milliliter at delivery and 19 (76%) had a viral load below 50 copies per milliliter. One child was perinatally HIV infected. Three women were exposed to EFV throughout the first 6 weeks of pregnancy. EFV was well tolerated, and among the 25 infants, no congenital anomalies or newborn complications were reported. Conclusions: Changes in EFV pharmacokinetics during pregnancy compared with postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy. Copyright © 2012 by Lippincott Williams & Wilkins.
format Journal
author Cressey T.
Stek A.
Capparelli E.
Bowonwatanuwong C.
Prommas S.
Sirivatanapa P.
Yuthavisuthi P.
Neungton C.
Huo Y.
Smith E.
Best B.
Mirochnick M.
spellingShingle Cressey T.
Stek A.
Capparelli E.
Bowonwatanuwong C.
Prommas S.
Sirivatanapa P.
Yuthavisuthi P.
Neungton C.
Huo Y.
Smith E.
Best B.
Mirochnick M.
Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum
author_facet Cressey T.
Stek A.
Capparelli E.
Bowonwatanuwong C.
Prommas S.
Sirivatanapa P.
Yuthavisuthi P.
Neungton C.
Huo Y.
Smith E.
Best B.
Mirochnick M.
author_sort Cressey T.
title Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum
title_short Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum
title_full Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum
title_fullStr Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum
title_full_unstemmed Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum
title_sort efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum
publishDate 2017
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84859758788&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/42883
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