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- W2288634103 abstract "Famciclovir is the oral form of penciclovir, a highly selective antiherpesvirus agent. Both famciclovir and penciclovir are being evaluated in clinical studies. This review covers the conversion of famciclovir to penciclovir, the formation and stability of penciclovir-triphosphate, its effect on herpesvirus DNA polymerases and the inhibition of viral DNA synthesis in cell cultures. The conversion of famciclovir into penciclovir is described, emphasising work with human tissues and including the elucidation of the structures of its chiral monoacetylated derivatives. To reflect its metabolism during oral absorption, famciclovir was incubated in duodenal contents, extracts of intestinal wall and liver, and in blood. The major metabolic route was by de-acetylation followed by oxidation of the purine to form penciclovir. This work with human tissues was predictive of the major metabolic pathway in humans. Penciclovir is phosphorylated much more efficiently than acyclovir in herpesvirus-infected cells yet the host cell kinases phosphorylate the two compounds to a small but comparable extent. This highly preferential metabolism in herpesvirus infected cells is a major factor in its selective antiviral activity. The ( S) enantiomer of penciclovir-triphosphate is the major metabolite and it has good stability in HSV-1, HSV-2, and VZV infected cells. At the high concentrations found in infected cells, penciclovir-triphosphate was an effective inhibitor of viral DNA polymerases and of viral DNA synthesis. The efficient entrapment of the active moiety can account for the markedly better antiviral activity of penciclovir than acyclovir when infected cell cultures were treated for a short time. Such assays reflect more closely the clinical situation after oral dosing than do standard assays in which the test compounds are present continuously. The role of these studies in compound selection and development is discussed." @default.
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- W2288634103 date "1993-04-01" @default.
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- W2288634103 title "Famciclovir and Penciclovir. The Mode of Action of Famciclovir Including Its Conversion to Penciclovir" @default.
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- W2288634103 doi "https://doi.org/10.1177/095632029300400201" @default.
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