A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women

© 2018 The Author(s) Background: Reducing the dose of efavirenz can improve safety, reduce costs, and increase access for patients with HIV infection. According to the World Health Organization, a similar dosing strategy for all patient populations is desirable for universal roll-out; however, it re...

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Main Authors: Stein Schalkwijk, Rob Ter Heine, Angela C. Colbers, Alwin D.R. Huitema, Paolo Denti, Kelly E. Dooley, Edmund Capparelli, Brookie M. Best, Tim R. Cressey, Rick Greupink, Frans G.M. Russel, Mark Mirochnick, David M. Burger
Format: Journal
Published: 2018
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85043397210&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/48481
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spelling th-cmuir.6653943832-484812018-04-25T10:12:57Z A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women Stein Schalkwijk Rob Ter Heine Angela C. Colbers Alwin D.R. Huitema Paolo Denti Kelly E. Dooley Edmund Capparelli Brookie M. Best Tim R. Cressey Rick Greupink Frans G.M. Russel Mark Mirochnick David M. Burger © 2018 The Author(s) Background: Reducing the dose of efavirenz can improve safety, reduce costs, and increase access for patients with HIV infection. According to the World Health Organization, a similar dosing strategy for all patient populations is desirable for universal roll-out; however, it remains unknown whether the 400 mg daily dose is adequate during pregnancy. Methods: We developed a mechanistic population pharmacokinetic model using pooled data from women included in seven studies (1968 samples, 774 collected during pregnancy). Total and free efavirenz exposure (AUC 24 and C 12 ) were predicted for 400 (reduced) and 600 mg (standard) doses in both pregnant and non-pregnant women. Results: Using a 400 mg dose, the median efavirenz total AUC 24 and C 12 during the third trimester of pregnancy were 91 and 87% of values among non-pregnant women, respectively. Furthermore, the median free efavirenz C 12 and AUC 24 were predicted to increase during pregnancy by 11 and 15%, respectively. Conclusions: It was predicted that reduced-dose efavirenz provides adequate exposure during pregnancy. These findings warrant prospective confirmation. 2018-04-25T10:12:57Z 2018-04-25T10:12:57Z 2018-03-08 Journal 11791926 03125963 2-s2.0-85043397210 10.1007/s40262-018-0642-9 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85043397210&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/48481
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description © 2018 The Author(s) Background: Reducing the dose of efavirenz can improve safety, reduce costs, and increase access for patients with HIV infection. According to the World Health Organization, a similar dosing strategy for all patient populations is desirable for universal roll-out; however, it remains unknown whether the 400 mg daily dose is adequate during pregnancy. Methods: We developed a mechanistic population pharmacokinetic model using pooled data from women included in seven studies (1968 samples, 774 collected during pregnancy). Total and free efavirenz exposure (AUC 24 and C 12 ) were predicted for 400 (reduced) and 600 mg (standard) doses in both pregnant and non-pregnant women. Results: Using a 400 mg dose, the median efavirenz total AUC 24 and C 12 during the third trimester of pregnancy were 91 and 87% of values among non-pregnant women, respectively. Furthermore, the median free efavirenz C 12 and AUC 24 were predicted to increase during pregnancy by 11 and 15%, respectively. Conclusions: It was predicted that reduced-dose efavirenz provides adequate exposure during pregnancy. These findings warrant prospective confirmation.
format Journal
author Stein Schalkwijk
Rob Ter Heine
Angela C. Colbers
Alwin D.R. Huitema
Paolo Denti
Kelly E. Dooley
Edmund Capparelli
Brookie M. Best
Tim R. Cressey
Rick Greupink
Frans G.M. Russel
Mark Mirochnick
David M. Burger
spellingShingle Stein Schalkwijk
Rob Ter Heine
Angela C. Colbers
Alwin D.R. Huitema
Paolo Denti
Kelly E. Dooley
Edmund Capparelli
Brookie M. Best
Tim R. Cressey
Rick Greupink
Frans G.M. Russel
Mark Mirochnick
David M. Burger
A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women
author_facet Stein Schalkwijk
Rob Ter Heine
Angela C. Colbers
Alwin D.R. Huitema
Paolo Denti
Kelly E. Dooley
Edmund Capparelli
Brookie M. Best
Tim R. Cressey
Rick Greupink
Frans G.M. Russel
Mark Mirochnick
David M. Burger
author_sort Stein Schalkwijk
title A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women
title_short A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women
title_full A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women
title_fullStr A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women
title_full_unstemmed A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women
title_sort mechanism-based population pharmacokinetic analysis assessing the feasibility of efavirenz dose reduction to 400 mg in pregnant women
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85043397210&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/48481
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