Famciclovir and Penciclovir

Famciclovir (Famvir) is the diacetyl ester prodrug of the acyclic guanosine analogue 6-deoxypenciclovir (Dena-vir). Penciclovir has activity against HSV-1, HSV-2, VZV, and HBV. After oral administration, famciclovir is converted to penciclovir by first-pass metabolism. Penciclovir has a mechanism of action similar to that of acyclovir. It is first monophosphorylated by viral thymi-dine kinase; then it is converted to a triphosphate by cellular kinases. Penciclovir triphosphate acts as a competitive inhibitor of viral DNA polymerase, but unlike acyclovir, it does not cause chain termination.

Mutations in DNA polymerase or thymidine kinase may result in resistance. Acyclovir-resistant HSV strains that exhibit thymidine kinase deficiency are also resistant to famciclovir and penciclovir.

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