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Genetic variation of kinases and activation of nucleotide analog reverse transcriptase inhibitor tenofovir.激酶的遗传变异和核苷酸类似物逆转录酶抑制剂替诺福韦的激活。
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2
Tenofovir or zidovudine in three-drug combination therapy with one nucleoside reverse transcriptase inhibitor and one non-nucleoside reverse transcriptase inhibitor for initial treatment of HIV infection in antiretroviral-naïve individuals.替诺福韦或齐多夫定与一种核苷类逆转录酶抑制剂及一种非核苷类逆转录酶抑制剂联合用于初治抗逆转录病毒治疗的人类免疫缺陷病毒感染个体的初始治疗。
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3
Tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of HIV infection.富马酸替诺福韦二吡呋酯：一种用于治疗HIV感染的核苷酸逆转录酶抑制剂。
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Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study.在标准一线抗逆转录病毒治疗方案失败的 HIV 患者中，经过 96 周利托那韦增强洛匹那韦加核苷或核苷酸逆转录酶抑制剂或拉替拉韦治疗后的身体成分和代谢结果：一项随机、开放标签、非劣效性 SECOND-LINE 研究的子研究。
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Comparative effectiveness of tenofovir in HIV-infected treatment-experienced patients: systematic review and meta-analysis.替诺福韦在接受过治疗的HIV感染患者中的比较疗效：系统评价和荟萃分析。
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Effect of alcohol exposure on the efficacy and safety of tenofovir alafenamide fumarate, a major medicine against human immunodeficiency virus.酒精暴露对富马酸替诺福韦艾拉酚胺酯（一种主要的抗人类免疫缺陷病毒药物）疗效和安全性的影响。
Biochem Pharmacol. 2022 Oct;204:115224. doi: 10.1016/j.bcp.2022.115224. Epub 2022 Aug 22.
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An open-label, randomized, single intravenous dosing study to investigate the effect of fixed-dose combinations of tenofovir/lamivudine or atazanavir/ritonavir on the pharmacokinetics of remdesivir in Ugandan healthy volunteers (RemTLAR).一项开放性、随机、单剂量静脉给药的研究，旨在探讨固定剂量组合替诺福韦/拉米夫定或阿扎那韦/利托那韦对乌干达健康志愿者中瑞德西韦药代动力学的影响（RemTLAR）。
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本文引用的文献

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MALDI Mass Spectrometry Imaging Reveals Heterogeneous Distribution of Tenofovir and Tenofovir Diphosphate in Colorectal Tissue of Subjects Receiving a Tenofovir-Containing Enema.基质辅助激光解吸电离飞行时间质谱成像揭示了接受含替诺福韦灌肠剂的受试者结直肠组织中替诺福韦及其二磷酸酯的不均匀分布。
J Pharmacol Exp Ther. 2018 Oct;367(1):40-48. doi: 10.1124/jpet.118.250357. Epub 2018 Jul 23.
2
Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women.随机、安慰剂对照的 I 期临床试验，评估了替诺福韦和替诺福韦加左炔诺孕酮阴道环在女性中的安全性、药代动力学、药效学和可接受性。
PLoS One. 2018 Jun 28;13(6):e0199778. doi: 10.1371/journal.pone.0199778. eCollection 2018.
3
Organ-Specific MicroRNAs ( and ) Contribute to Tissue Characteristics and Carcinogenesis by Regulating Pyruvate Kinase M1/2 () Expression.器官特异性 microRNAs (miRNAs) 通过调节丙酮酸激酶 M1/2 (PKM) 的表达来影响组织特征和癌症发生。
Int J Mol Sci. 2018 Apr 24;19(5):1276. doi: 10.3390/ijms19051276.
4
Discovery of genetic variants of the kinases that activate tenofovir among individuals in the United States, Thailand, and South Africa: HPTN067.在美国、泰国和南非人群中发现激活替诺福韦的激酶的遗传变异体：HPTN067。
PLoS One. 2018 Apr 11;13(4):e0195764. doi: 10.1371/journal.pone.0195764. eCollection 2018.
5
Genetic Variation of the Kinases That Phosphorylate Tenofovir and Emtricitabine in Peripheral Blood Mononuclear Cells.外周血单个核细胞中磷酸化替诺福韦和恩曲他滨的激酶的基因变异
AIDS Res Hum Retroviruses. 2018 May;34(5):421-429. doi: 10.1089/AID.2017.0243. Epub 2018 Mar 20.
6
Recent advances in understanding the pathogenesis and management of reticular dysgenesis.网状发育不良发病机制和治疗的最新进展。
Br J Haematol. 2018 Mar;180(5):644-653. doi: 10.1111/bjh.15045. Epub 2017 Dec 21.
7
Discovery of novel naphthoquinone derivatives as inhibitors of the tumor cell specific M2 isoform of pyruvate kinase.发现新型萘醌衍生物作为肿瘤细胞特异性丙酮酸激酶 M2 同工酶的抑制剂。
Eur J Med Chem. 2017 Sep 29;138:343-352. doi: 10.1016/j.ejmech.2017.06.064. Epub 2017 Jun 29.
8
Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study.从依非韦伦、恩曲他滨和富马酸替诺福韦二吡呋酯转换为替诺福韦艾拉酚胺与利匹韦林和恩曲他滨联合复方制剂用于治疗 HIV-1 感染病毒抑制成人：一项随机、双盲、多中心、3b 期、非劣效性研究。
Lancet HIV. 2017 May;4(5):e205-e213. doi: 10.1016/S2352-3018(17)30032-2. Epub 2017 Mar 2.
9
Creatine kinase in ischemic and inflammatory disorders.缺血性和炎症性疾病中的肌酸激酶
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10
Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population.泰国人群中丙酮酸激酶（PKLR）变体对疟疾表型的调节作用
PLoS One. 2015 Dec 14;10(12):e0144555. doi: 10.1371/journal.pone.0144555. eCollection 2015.

激酶的遗传变异和核苷酸类似物逆转录酶抑制剂替诺福韦的激活。

Genetic variation of kinases and activation of nucleotide analog reverse transcriptase inhibitor tenofovir.

机构信息

Department of Medicine (Division of Clinical Pharmacology), Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

出版信息

Pharmacogenomics. 2019 Jan;20(2):105-111. doi: 10.2217/pgs-2018-0140. Epub 2019 Jan 10.

DOI:10.2217/pgs-2018-0140
PMID:30628547
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6563221/
Abstract

As antiretroviral therapy has become more accessible across the world and coformulations have improved patient compliance; the morbidity and mortality of HIV/AIDS has decreased. However, there is still a substantial gap in knowledge regarding the impact of genetic variation on the metabolism of and response to some of the most commonly prescribed antiretrovirals, including the nucleotide reverse transcriptase inhibitor tenofovir. While it has been scientifically established that tenofovir must be activated to be efficacious against HIV, the enzymes responsible for this activation have not been well characterized. The purpose of this review is to summarize and clarify the scientific knowledge regarding the enzymes that phosphorylate and activate this clinically important drug.

摘要

随着抗逆转录病毒疗法在全球范围内的普及和复方制剂提高了患者的依从性，艾滋病毒/艾滋病的发病率和死亡率已经下降。然而，对于遗传变异对一些最常用的抗逆转录病毒药物（包括核苷酸逆转录酶抑制剂替诺福韦）的代谢和反应的影响，仍存在很大的知识差距。虽然已经从科学上确定替诺福韦必须被激活才能有效地对抗艾滋病毒，但负责这种激活的酶尚未得到很好的描述。本综述的目的是总结和澄清有关使这种临床重要药物磷酸化和激活的酶的科学知识。