Snopková Svatava, Havlíčková Kateřina, Husa Petr
Department of Infectious Disease, Faculty of Medicine and University Hospital, Masaryk University, Brno, Czech Republic, e-mail:
Klin Mikrobiol Infekc Lek. 2016 Sep;22(3):111-117.
Antiretroviral therapy as a life-long treatment has to meet the criteria of maximum efficiency while maintaining the highest possible level of safety and tolerance. Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug with an excellent effect of virological suppression. However, some patients can over time develop clinically significant nephrotoxicity or bone loss. Tenofovir alafenamide fumarate (TAF) is a novel prodrug of tenofovir (TFV) that is more stable in human plasma and more efficiently penetrates into target cells than TFV. Tenofovir converted from TAF reaches plasma concentration which is 90% lower than that of TFV converted from TDF. Conversely, the active metabolite converted from TAF reaches a higher intracellular level in target cells than TFV from TDF. This allows a substantial reduction of its oral dose, decreasing the risk for renal and bone toxicity. It is even possible to reduce the dose of TAF in case it is administered concurrently with cobicistat further improving its absorption and optimizing its pharmacokinetic profile. Pharmacokinetic properties are another factor substantially influencing its safety profile. TAF is not a substrate for renal organic anion transporters and thus shows no cytotoxicity related to their expression. Based on clinical trials, a fixed-dose combination tablet (single-tablet regimen) containing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate was approved by the FDA in November 2015. This regimen showed higher efficacy, better safety profile and tolerance than TDF-based regiments. Recently, it has been approved in European Union countries.
抗逆转录病毒疗法作为一种终身治疗方法，必须在保持尽可能高的安全性和耐受性水平的同时，满足最大疗效的标准。替诺福韦酯（TDF）是一种具有出色病毒学抑制效果的抗逆转录病毒药物。然而，随着时间的推移，一些患者可能会出现具有临床意义的肾毒性或骨质流失。替诺福韦艾拉酚胺富马酸盐（TAF）是替诺福韦（TFV）的一种新型前体药物，在人血浆中更稳定，比TFV更有效地渗透到靶细胞中。从TAF转化而来的替诺福韦达到的血浆浓度比从TDF转化而来的TFV低90%。相反，从TAF转化而来的活性代谢物在靶细胞中达到的细胞内水平高于从TDF转化而来的TFV。这使得其口服剂量大幅降低，降低了肾毒性和骨毒性的风险。如果TAF与考比司他同时给药，甚至有可能降低TAF的剂量，进一步改善其吸收并优化其药代动力学特征。药代动力学特性是另一个对其安全性有重大影响的因素。TAF不是肾脏有机阴离子转运体的底物，因此未显示出与其表达相关的细胞毒性。基于临床试验，一种含有埃替格韦/考比司他/恩曲他滨/替诺福韦艾拉酚胺富马酸盐的固定剂量复方片剂（单片方案）于2015年11月获得美国食品药品监督管理局（FDA）批准。该方案显示出比基于TDF的方案更高的疗效、更好的安全性和耐受性。最近，它已在欧盟国家获得批准。
