Tenofovir alafenamide (TAF) clinical pharmacology

Abstract

Tenofovir today exists in two pharmaceutical forms, such as Tenofovir disoproxil fumarate (TDF) and the newer Tenofovir alafenamide (TAF). The two different salts are required in order to promote intestinal absorption of the active molecule (TFV). Once absorbed the distribution of TFV into compartments is driven by the salt to which the drug is conjugated; in case of TDF, following absorption most of TFV is cleared from its link with the salt and the drug is widely distributed into different tissues, while in case of TAF the reverse is true as TFV remains mostly associated to its alafenamide salt and its distribution is restricted to cells with high carboxyesterase and catepsin A activity, such as hepatocytes and lymphocytes. This generates higher plasma levels of TFV in case of TDF while in the case of TFV much higher intracellular concentrations in target cells are achieved. The main reason for TAF development was to reduce the impact of the drug on proximal renal function and this was actually obtained by the much lower plasma concentration of TFV. Numerous clinical trials consistently demonstrated the significant lesser impact of TAF vs TDF on both renal function and structural bone integrity.

Keywords: Low-molecular weight protein; Proximal renal tubule; Tenfovir alafenamide (TAF); Tenofovir (TFV); Tenofovir disoproxil fumarate (TDF).