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Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV

The purpose of this study was to investigate the impact of CYP2B6‐G516T polymorphisms on the pharmacokinetics (PKs) of efavirenz among the Chinese population and to propose doses for different genotypic populations that optimize therapeutic outcomes. Nonlinear mixed‐effect modeling was applied to de...

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Detalles Bibliográficos
Autores principales: Hui, KH, Lee, SS, Lam, TN
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846779/
https://www.ncbi.nlm.nih.gov/pubmed/27299708
http://dx.doi.org/10.1002/psp4.12067
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author Hui, KH
Lee, SS
Lam, TN
author_facet Hui, KH
Lee, SS
Lam, TN
author_sort Hui, KH
collection PubMed
description The purpose of this study was to investigate the impact of CYP2B6‐G516T polymorphisms on the pharmacokinetics (PKs) of efavirenz among the Chinese population and to propose doses for different genotypic populations that optimize therapeutic outcomes. Nonlinear mixed‐effect modeling was applied to describe PKs of efavirenz in Chinese patients with human immunodeficiency virus (HIV). Probabilities of successful treatment at different doses were obtained by simulations using the developed model to identify the optimal doses. The model was based on data from 163 individuals. Efavirenz clearance was found to be significantly influenced by CYP2B6‐G516T polymorphisms and body weight. The typical values of oral clearance were 10.2 L/h, 7.33 L/h, and 2.38 L/h and simulation results suggested that the optimal daily oral doses are 550 mg, 350 mg, and 100 mg for the GG, GT, and TT populations, respectively. The effect of CYP2B6‐G516T polymorphisms on efavirenz clearance was successfully quantified. Pharmacogenetics‐based dose individualization of efavirenz may optimize patient outcomes by promoting efficacy while minimizing central nervous system (CNS) side effects.
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spelling pubmed-48467792016-12-12 Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV Hui, KH Lee, SS Lam, TN CPT Pharmacometrics Syst Pharmacol Original Articles The purpose of this study was to investigate the impact of CYP2B6‐G516T polymorphisms on the pharmacokinetics (PKs) of efavirenz among the Chinese population and to propose doses for different genotypic populations that optimize therapeutic outcomes. Nonlinear mixed‐effect modeling was applied to describe PKs of efavirenz in Chinese patients with human immunodeficiency virus (HIV). Probabilities of successful treatment at different doses were obtained by simulations using the developed model to identify the optimal doses. The model was based on data from 163 individuals. Efavirenz clearance was found to be significantly influenced by CYP2B6‐G516T polymorphisms and body weight. The typical values of oral clearance were 10.2 L/h, 7.33 L/h, and 2.38 L/h and simulation results suggested that the optimal daily oral doses are 550 mg, 350 mg, and 100 mg for the GG, GT, and TT populations, respectively. The effect of CYP2B6‐G516T polymorphisms on efavirenz clearance was successfully quantified. Pharmacogenetics‐based dose individualization of efavirenz may optimize patient outcomes by promoting efficacy while minimizing central nervous system (CNS) side effects. John Wiley and Sons Inc. 2016-04-06 2016-04 /pmc/articles/PMC4846779/ /pubmed/27299708 http://dx.doi.org/10.1002/psp4.12067 Text en © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Hui, KH
Lee, SS
Lam, TN
Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV
title Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV
title_full Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV
title_fullStr Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV
title_full_unstemmed Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV
title_short Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV
title_sort dose optimization of efavirenz based on individual cyp2b6 polymorphisms in chinese patients positive for hiv
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846779/
https://www.ncbi.nlm.nih.gov/pubmed/27299708
http://dx.doi.org/10.1002/psp4.12067
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