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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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 |
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© 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. |
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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 |
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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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1681423256940183552 |