Drug Evaluations: Drug Evaluation Anti-infectives: Famciclovir - origins, progress and prospects

Abstract

Famciclovir (FAMVIRd˚) is an oral prodrug which provides penciclovir with high bioavailability. Penciclovir is a guanosine-based nucleoside analogue which is structurally related to aciclovir and ganciclovir. Penciclovir is highly active against herpes simplex virus (types 1 and 2), varicella zoster virus, and human hepatitis B virus. The mechanism of herpesvirus inhibition is similar to that of aciclovir in that penciclovir is phosphorylated selectively in virus-infected cells by virus-coded thymidine kinase; the nucleoside analogue triphosphate is then a selective inhibitor of herpesvirus DNA polymerase. The relative affinities of aciclovir and penciclovir triphosphate are, however, markedly different for the two virus-coded enzymes; moreover penciclovir triphosphate has a significantly longer half-life in virus-infected cells than the corresponding triphosphate of aciclovir. These subtle biochemical differences are reflected in striking differences between the compounds revealed in laboratory infection...