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Establishment of intracellular tenofovir-diphosphate as the key determinant for in vitro-in vivo translation of antiviral efficacy
Antiviral Research ( IF 4.5 ) Pub Date : 2018-01-11 , DOI: 10.1016/j.antiviral.2018.01.005
Bennett Ma 1 , Aline Barth 1 , Carolyn M McHale 2 , Ming-Tain Lai 2
Affiliation  

In vitro evaluation of tenofovir disproxil fumarate (TDF) and tenofovir alafenamide (TAF) revealed comparable antiviral effects with respect to the tenofovir-diphosphate (TFV-DP) level in human peripheral blood mononuclear cells (PBMCs), despite the EC50 values determined based on prodrug concentrations were nearly two orders of magnitude apart. In vivo EC50 obtained from meta-analyses were in good agreement with the in vitro results, indicating intracellular TFV-DP can be employed for in vitro-in vivo translation of viral inhibition for tenofovir prodrugs. Current analysis indicated that the intracellular concentrations of TFV-DP achieving maximal antiviral effect in vitro can be directly translatable in the clinic to accomplish maximal viral load suppression attainable by tenofovir-prodrugs.



中文翻译:

建立细胞内替诺福韦-二磷酸作为抗病毒药效体外-体内翻译的关键决定因素

富诺酸替诺福韦酯(TDF)和替诺福韦阿拉芬酰胺(TAF)的体外评估显示,尽管确定的EC 50值为基础,但人类外周血单核细胞(PBMC)中的替诺福韦二磷酸(TFV-DP)水平具有可比的抗病毒作用前药的浓度相差近两个数量级。体内EC 50从荟萃分析获得的结果与体外结果高度吻合,表明细胞内TFV-DP可用于替诺福韦前药的病毒抑制作用的体外-体内翻译。目前的分析表明,在体外达到最大抗病毒作用的TFV-DP的细胞内浓度可在临床上直接翻译,以实现替诺福韦前药可实现的最大病毒载量抑制。

更新日期:2018-01-11
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