<p>Tenofovir alafenamide is a phosphonamidate&nbsp;prodrug&nbsp;of tenofovir (2&#39;-deoxyadenosine monophosphate analog). Tenofovir alafenamide as a lipophilic cell-permeant compound enters primary hepatocytes by passive diffusion and by the hepatic uptake transporters OATP1B1 and OATP1B3. Tenofovir alafenamide is then converted to tenofovir through hydrolysis primarily by carboxylesterase 1 (CES1) in primary hepatocytes. Intracellular tenofovir is subsequently phosphorylated by cellular kinases to the pharmacologically active metabolite tenofovir diphosphate. Tenofovir diphosphate inhibits&nbsp;HBV&nbsp;replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain-termination.<br />
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Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases that include&nbsp;mitochondrial DNA polymerase &gamma; and there is no evidence of toxicity to&nbsp;mitochondria&nbsp;in cell culture.</p>