Pharmacokinetics, Pharmacodynamics and Drug Metabolism, MSD, West Point, PA, 19486, USA.
Pharmacokinetics, Pharmacodynamics and Drug Metabolism, MSD, West Point, PA, 19486, USA.
Antiviral Res. 2018 Mar;151:1-3. doi: 10.1016/j.antiviral.2018.01.005. Epub 2018 Jan 11.
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 EC values determined based on prodrug concentrations were nearly two orders of magnitude apart. In vivo EC 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.
体外评价富马酸替诺福韦二吡呋酯（TDF）和替诺福韦艾拉酚胺（TAF）发现，尽管基于前药浓度确定的 EC 值相差近两个数量级，但在人外周血单核细胞（PBMC）中，其与替诺福韦二磷酸（TFV-DP）水平的抗病毒效果相当。荟萃分析得出的体内 EC 值与体外结果吻合较好，提示细胞内 TFV-DP 可用于替诺福韦前药的病毒抑制从体外到体内的转化。目前的分析表明，在体外达到最大抗病毒效果的细胞内 TFV-DP 浓度可直接转化为临床，以实现替诺福韦前药所能达到的最大病毒载量抑制。
