依非韦伦在 HIV 感染治疗中的应用。
Efavirenz in the therapy of HIV infection.
机构信息
The George Washington University, School of Medicine and Health Sciences, Department of Pediatrics, and Special Immunology Program, Children's National Medical Center, Division of Infectious Disease, Washington, DC 20010, USA.
出版信息
Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):95-103. doi: 10.1517/17425250903483207.
IMPORTANCE OF THE FIELD
The use of the first generation non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) as a component of first-line antiretroviral therapy has been accepted worldwide. EFV is the only antiretroviral agent currently on the market that has been combined with emtricitabine and tenofovir disoproxil fumarate in a single tablet and administered once daily.
AREAS COVERED IN THIS REVIEW
This article reviews efficacy and safety data on EFV and the role of pharmacogenetics in EFV exposure. Published articles and conference presentations on EFV are reviewed.
WHAT THE READER WILL GAIN
CYP2B6 genetic polymorphisms influence the metabolism of EFV. The CYP2B6 G to T polymorphism at position 516 is shown to be associated with elevated plasma concentrations and an increase in neurotoxicity of EFV, while the wild-type genotype has been associated with sub-therapeutic concentrations of EFV, potentially leading to the development of viral resistance. This polymorphism is significantly higher in sub-Saharan Africans and African Americans as compared to Hispanic, European and Asian populations.
TAKE HOME MESSAGE
The significance of CYP2B6 polymorphism in EFV exposure indicates the need for prospective clinical studies to evaluate the utility of genotype-driven dose adjustments in populations of diverse descent.
重要性领域
第一代非核苷类逆转录酶抑制剂依非韦伦（EFV）作为一线抗逆转录病毒治疗的组成部分，已在全球范围内得到认可。EFV 是目前市场上唯一一种与恩曲他滨和替诺福韦二吡呋酯联合制成单片、每日一次给药的抗逆转录病毒药物。
本文综述了 EFV 的疗效和安全性数据，以及药物遗传学在 EFV 暴露中的作用。对 EFV 的已发表文章和会议报告进行了回顾。
读者将获得的收益
CYP2B6 基因多态性影响 EFV 的代谢。CYP2B6 516 位 G 到 T 点的多态性与血浆浓度升高和 EFV 的神经毒性增加有关，而野生型基因型与 EFV 的治疗浓度降低有关，这可能导致病毒耐药性的产生。与西班牙裔、欧洲裔和亚裔人群相比，这种多态性在撒哈拉以南非洲人和非裔美国人中明显更高。
需要注意的是
CYP2B6 多态性对 EFV 暴露的意义表明，需要前瞻性临床研究来评估在不同种族人群中，基于基因型的剂量调整的效用。
Zotero 插件