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The metabolism of acyclovir to its mono-, di-, and triphosphate derivatives was examined in uninfected and virus-infected cells. The level of phosphorylation of acyclovir was dependent upon virus type, cell line, exogenous drug concentration, and exposure time. Acyclovir phosphorylation was inhibited by exogenously added nucleosides. The order of inhibition was deoxythymidine greater than deoxycytidine greater than guanosine greater than or equal to deoxyguanosine. Acyclovir triphosphate persisted in infected cells after removal of the drug from the medium. The initial half-life of the triphosphate was 1.2 h in the absence of the drug in the medium, but triphosphate levels reached a plateau after 6 h. The presence of low concentrations of the drug in the medium resulted in a longer persistence of the intracellular triphosphate and a higher plateau level.
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