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 models. In man, the clinical data to date suggest that famciclovir has a good safety profile and there are grounds for optimism that the compound will provide opportunities for improved efficacy for the treatment of herpes simplex and varicella zoster virus infections.

(åFAMVIR is a trademark of SmithKline Beecham plc)

Key Words:

• aciclovir
• acyclovir
• antiviral chemotherapy
• duck hepatitis B virus
• famciclovir
• hepatitis B virus
• herpes simplex virus
• nucleoside analogue
• penciclovir
• prodrug
• valaciclovir
• varicella-zoster virus