Pharmacokinetics, pharmacodynamics, and pharmacogenetics of Efavirenz 400 mg once daily during pregnancy and post-partum

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Title: Pharmacokinetics, pharmacodynamics, and pharmacogenetics of Efavirenz 400 mg once daily during pregnancy and post-partum
Author(s): Lamorde, M
Wang, X
Neary, M
Bisdomini, E
Nakalema, S
Byakika-Kibwika, P
Mukonzo, JK
Khan, W
Owen, A
McClure, M
Boffito, M
Item Type: Journal Article
Abstract: Background A clinical trial showed that efavirenz 400 mg once daily (EFV400) is as effective as the standard adult dose. World Health Organization recommends EFV400 as an alternative first-line agent, but data are lacking in the third trimester of pregnancy (TT). We investigated the pharmacokinetics, efficacy, and CYP2B6 pharmacogenetics in HIV-infected women (WLWH) on EFV400 during TT and post-partum (PP). Methods An open-label 2-center study (United Kingdom, Uganda) was conducted in WLWH receiving antiretroviral regimens containing efavirenz 600 mg, who had their efavirenz dose reduced to EFV400. Weekly therapeutic drug monitoring (TDM), steady-state pharmacokinetic profiles (TT and PP), safety, virological efficacy, and CYP2B6 polymorphisms at positions 516 (C > T) and 938 (T > C) were evaluated. Results Twenty-five WLWH of African origin were enrolled. All had viral loads <50 copies/mL at baseline, which were maintained throughout the study. No infant was HIV infected. No WLWH were withdrawn due to low EFV400 TDM results. Geometric mean ratios (TT/PP; 90% confidence interval) for EFV400 maximum observed plasma concentration, area under the curve, and plasma concentration measured 24 hours after the observed dose were 0.97 (.85–1.10), 0.87 (.76–.99), and 0.77 (.65–.91), respectively. Five of 25 WLWH were slow metabolizers. Conclusions Although EFV400 pharmacokinetic parameters were slightly lower for TT compared with PP values, efavirenz concentrations exceeded cutoff levels established by the study and those measured in antiretroviral-naive patients receiving EFV400 in ENCORE1. All subjects maintained a viral load <50 copies/mL, suggesting that EFV400 can be used in pregnant WLWH.
Publication Date: 1-Sep-2018
Date of Acceptance: 22-Feb-2018
URI: http://hdl.handle.net/10044/1/63109
DOI: https://dx.doi.org/10.1093/cid/ciy161
ISSN: 1058-4838
Publisher: Oxford University Press (OUP)
Start Page: 785
End Page: 790
Journal / Book Title: Clinical Infectious Diseases
Volume: 67
Issue: 5
Copyright Statement: © 2018 Oxford University Press. This is a pre-copy-editing, author-produced version of an article accepted for publication in Clinical Infectious Diseases following peer review. The definitive publisher-authenticated version Mohammed Lamorde, Xinzhu Wang, Megan Neary, Elisa Bisdomini, Shadia Nakalema, Pauline Byakika-Kibwika, Jackson K Mukonzo, Waheed Khan, Andrew Owen, Myra McClure, Marta Boffito; Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics of Efavirenz 400 mg Once Daily During Pregnancy and Post-Partum, Clinical Infectious Diseases, Volume 67, Issue 5, 16 August 2018, Pages 785–790, is available online at: https://dx.doi.org/10.1093/cid/ciy161
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
low-dose efavirenz
pharmacokinetics
pregnancy
HIV-INFECTED PATIENTS
DOSE OPTIMIZATION
PROTEIN-BINDING
PLASMA
ENCORE1
DRUGS
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
low-dose efavirenz
pharmacokinetics
pregnancy
HIV-INFECTED PATIENTS
DOSE OPTIMIZATION
PROTEIN-BINDING
PLASMA
ENCORE1
DRUGS
06 Biological Sciences
11 Medical And Health Sciences
Microbiology
Publication Status: Published
Online Publication Date: 2018-02-23
Appears in Collections:Department of Medicine
Faculty of Medicine



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