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1
The Pharmacogenetics of Efavirenz Metabolism in Children: The Potential Genetic and Medical Contributions to Child Development in the Context of Long-Term ARV Treatment.儿童中依非韦伦代谢的药物遗传学:长期抗逆转录病毒治疗背景下对儿童发育的潜在遗传和医学贡献。
New Dir Child Adolesc Dev. 2020 May;2020(171):107-133. doi: 10.1002/cad.20353. Epub 2020 Jul 12.
2
Dosage Optimization of Efavirenz Based on a Population Pharmacokinetic-Pharmacogenetic Model of HIV-infected Patients in Thailand.基于泰国 HIV 感染患者群体药代动力学-药效遗传学模型的依非韦伦剂量优化。
Clin Ther. 2020 Jul;42(7):1234-1245. doi: 10.1016/j.clinthera.2020.04.013. Epub 2020 May 22.
3
Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation.病例报告:儿童中与依非韦伦代谢异常相关的严重中枢神经系统表现:CYP2B6基因变异的作用
BMC Infect Dis. 2016 Feb 2;16:56. doi: 10.1186/s12879-016-1381-x.
4
Pharmacokinetic and Pharmacodynamic Comparison of Once-Daily Efavirenz (400 mg vs. 600 mg) in Treatment-Naïve HIV-Infected Patients: Results of the ENCORE1 Study.初治HIV感染患者每日一次依非韦伦(400毫克与600毫克)的药代动力学和药效学比较:ENCORE1研究结果
Clin Pharmacol Ther. 2015 Oct;98(4):406-16. doi: 10.1002/cpt.156. Epub 2015 Jul 14.
5
Efavirenz Metabolism: Influence of Polymorphic CYP2B6 Variants and Stereochemistry.依非韦伦代谢:多态 CYP2B6 变体和立体化学的影响。
Drug Metab Dispos. 2019 Oct;47(10):1195-1205. doi: 10.1124/dmd.119.086348. Epub 2019 Jul 19.
6
CYP2B6 genotype-directed dosing is required for optimal efavirenz exposure in children 3-36 months with HIV infection.对于3至36个月大的HIV感染儿童,需要根据CYP2B6基因型指导用药,以实现依非韦伦的最佳暴露量。
AIDS. 2017 May 15;31(8):1129-1136. doi: 10.1097/QAD.0000000000001463.
7
Genetic variants in CYP2B6 and CYP2A6 explain interindividual variation in efavirenz plasma concentrations of HIV-infected children with diverse ethnic origin.CYP2B6和CYP2A6基因变异解释了不同种族来源的HIV感染儿童中依非韦伦血浆浓度的个体间差异。
PLoS One. 2017 Sep 8;12(9):e0181316. doi: 10.1371/journal.pone.0181316. eCollection 2017.
8
Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele.巴布亚新几内亚艾滋病毒/艾滋病患者的血浆依非韦伦浓度存在较大差异,与 CYP2B6 516T 等位基因的高频率相关。
Clin Transl Sci. 2021 Nov;14(6):2521-2531. doi: 10.1111/cts.13120. Epub 2021 Aug 20.
9
Efavirenz in the therapy of HIV infection.依非韦伦在 HIV 感染治疗中的应用。
Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):95-103. doi: 10.1517/17425250903483207.
10
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-Containing Antiretroviral Therapy.临床药物遗传学实施联盟(CPIC)指南:CYP2B6 和含依非韦伦的抗逆转录病毒治疗。
Clin Pharmacol Ther. 2019 Oct;106(4):726-733. doi: 10.1002/cpt.1477. Epub 2019 Jul 5.

本文引用的文献

1
Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV.利用治疗药物监测数据优化儿童抗逆转录病毒药物的给药建议和治疗管理,以治疗 HIV 感染者。
Ther Drug Monit. 2019 Aug;41(4):431-443. doi: 10.1097/FTD.0000000000000637.
2
Adverse Neuropsychiatric Events and Recreational Use of Efavirenz and Other HIV-1 Antiretroviral Drugs.抗反转录病毒药物依非韦伦及其他药物的神经精神不良事件与娱乐性使用。
Pharmacol Rev. 2018 Jul;70(3):684-711. doi: 10.1124/pr.117.013706.
3
Pharmacogenetic associations with cytochrome P450 in antiretroviral therapy: what does the future hold?抗逆转录病毒治疗中细胞色素 P450 的药物遗传学相关性:未来如何?
Expert Opin Drug Metab Toxicol. 2018 Jun;14(6):601-611. doi: 10.1080/17425255.2018.1478964. Epub 2018 May 28.
4
Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes.博茨瓦纳人类细胞色素 P450 2B6 遗传多态性:单倍型多样性和趋同表型的案例。
Sci Rep. 2018 Mar 20;8(1):4912. doi: 10.1038/s41598-018-23350-1.
5
Genetic variants in CYP2B6 and CYP2A6 explain interindividual variation in efavirenz plasma concentrations of HIV-infected children with diverse ethnic origin.CYP2B6和CYP2A6基因变异解释了不同种族来源的HIV感染儿童中依非韦伦血浆浓度的个体间差异。
PLoS One. 2017 Sep 8;12(9):e0181316. doi: 10.1371/journal.pone.0181316. eCollection 2017.
6
Sub-therapeutic nevirapine concentration during antiretroviral treatment initiation among children living with HIV: Implications for therapeutic drug monitoring.HIV感染儿童开始抗逆转录病毒治疗期间奈韦拉平浓度低于治疗水平:对治疗药物监测的影响
PLoS One. 2017 Aug 21;12(8):e0183080. doi: 10.1371/journal.pone.0183080. eCollection 2017.
7
CYP2B6 Haplotype Predicts Efavirenz Plasma Concentration in Black South African HIV-1-Infected Children: A Longitudinal Pediatric Pharmacogenomic Study.CYP2B6单倍型预测南非黑人HIV-1感染儿童的依非韦伦血浆浓度:一项纵向儿科药物基因组学研究。
OMICS. 2017 Aug;21(8):465-473. doi: 10.1089/omi.2017.0078.
8
Impact of Single Nucleotide Polymorphisms on Plasma Concentrations of Efavirenz and Lopinavir/Ritonavir in Chinese Children Infected with the Human Immunodeficiency Virus.中国人类免疫缺陷病毒感染儿童中,单核苷酸多态性对依非韦伦和洛匹那韦/利托那韦血药浓度的影响。
Pharmacotherapy. 2017 Sep;37(9):1073-1080. doi: 10.1002/phar.1988. Epub 2017 Sep 3.
9
Efavirenz: What is known about the cellular mechanisms responsible for its adverse effects.依非韦伦:关于其不良反应的细胞机制有哪些已知信息。
Eur J Pharmacol. 2017 Oct 5;812:163-173. doi: 10.1016/j.ejphar.2017.07.016. Epub 2017 Jul 8.
10
CYP2B6 genotype-directed dosing is required for optimal efavirenz exposure in children 3-36 months with HIV infection.对于3至36个月大的HIV感染儿童,需要根据CYP2B6基因型指导用药,以实现依非韦伦的最佳暴露量。
AIDS. 2017 May 15;31(8):1129-1136. doi: 10.1097/QAD.0000000000001463.

儿童中依非韦伦代谢的药物遗传学:长期抗逆转录病毒治疗背景下对儿童发育的潜在遗传和医学贡献。

The Pharmacogenetics of Efavirenz Metabolism in Children: The Potential Genetic and Medical Contributions to Child Development in the Context of Long-Term ARV Treatment.

机构信息

University of Houston.

Durham University.

出版信息

New Dir Child Adolesc Dev. 2020 May;2020(171):107-133. doi: 10.1002/cad.20353. Epub 2020 Jul 12.

DOI:10.1002/cad.20353
PMID:32657046
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9015892/
Abstract

Efavirenz (EFV) is a well-known, effective anti-retroviral drug long used in first-line treatment for children and adults with HIV and HIV/AIDS. Due to its narrow window of effective concentrations, between 1 and 4 μg/mL, and neurological side effects at supratherapeutic levels, several investigations into the pharmacokinetics of the drug and its genetic underpinnings have been carried out, primarily with adult samples. A number of studies, however, have examined the genetic influences on the metabolism of EFV in children. Their primary goal has been to shed light on issues of appropriate pediatric dosing, as well as the manifestation of neurotoxic effects of EFV in some children. Although EFV is currently being phased out of use for the treatment of both adults and children, we share this line of research to highlight an important aspect of medical treatment that is relevant to understanding the development of children diagnosed with HIV.

摘要

依非韦伦(EFV)是一种众所周知的、有效的抗逆转录病毒药物,长期以来一直用于治疗儿童和成人 HIV 及艾滋病的一线治疗。由于其有效浓度范围狭窄,在 1 至 4μg/ml 之间,且在治疗水平以上具有神经副作用,因此对该药的药代动力学及其遗传基础进行了多项研究,主要是使用成人样本进行的。然而,有许多研究检查了 EFV 在儿童体内代谢的遗传影响。他们的主要目标是阐明适当的儿科剂量问题,以及 EFV 在某些儿童中产生神经毒性作用的表现。尽管 EFV 目前已逐步退出成人和儿童的治疗应用,但我们分享这一系列研究,旨在强调与理解诊断为 HIV 的儿童的治疗发展相关的一个重要方面。