Comparison of the in vitro and in vivo anti-herpes activities of 1-beta-D-arabinofuranosylthymine and its 5'-monophosphate.

In vitro and in vivo anti-herpes activities of 1-beta-D-arabinofuranosylthymine 5'-monophosphate (ara-TMP) were compared with those of 1-beta-D-arabinofuranosylthymine (ara-T). On a molar basis ara-TMP was almost as active as ara-T against six strains of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) as monitored by a cytopathogenicity-inhibition and a plaque reduction assay in human embryonic lung fibroblast cells. When tested against experimental encephalitis in mice inoculated intracerebrally with HSV-1, intraperitoneal or intravenous treatment with 150 mg/kg/day of ara-TMP or 100 mg/kg/day of ara-T, for 5 days was effective in increasing in the mean survival time of mice. For a single dose of ara-TMP, intravenous administration was more effective than intraperitoneal or oral administration. However, oral administration of ara-T was the most effective of the treatment regimens used. Substantial plasma levels of ara-T were detected for a longer time after oral administration of ara-T than after intravenous administration of ara-TMP or ara-T, suggesting that the efficacy of oral administration of ara-T may be correlated with the maintenance of the substantial blood drug levels.