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Famciclovir: An overview

INTRODUCTION

Famciclovir  is an oral prodrug which is converted by first-pass metabolism to the antiviral drug penciclovir [1,2].

MECHANISM OF ACTION

Penciclovir, upon intracellular uptake, is monophosphorylated by virally-encoded thymidine kinase and, subsequently, converted to a triphosphate by cellular enzymes. Penciclovir triphosphate preferentially inhibits the DNA polymerase of susceptible viruses; at clinically relevant levels, there is no substantial effect upon cellular DNA polymerase, thereby minimizing side effects to the host [2].

This mechanism is similar to that described for acyclovir; however, compared to acyclovir triphosphate, penciclovir triphosphate has a lower affinity for viral DNA polymerase but a longer intracellular half-life [2]. (See "Acyclovir: An overview".)

Spectrum of activity — Penciclovir is active against herpes simplex virus (HSV) types 1 and 2, and varicella-zoster virus (VZV). Clinical utility against hepatitis B virus is under investigation, and Epstein-Barr virus is also susceptible in vitro [2].

Mechanism of resistance — The mechanisms of resistance to penciclovir are similar to those described for acyclovir [3]. Three mechanisms have been shown to endow herpes simplex viruses with resistance to acyclovir, a phenomenon rare in the immunocompetent host [4]:
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