Activity of Famciclovir and Penciclovir in HSV-Infected Animals: A Review

Penciclovir is a potent and highly selective antiherpesvirus agent. Both penciclovir and its oral form, famciclovir, are being evaluated in clinical studies. The activity of penciclovir and famciclovir against herpes simplex virus types 1 and 2 (HSV-1, HSV-2) infections in animals is reviewed. Penciclovir showed potent activity in a variety of cutaneous, genital and systemic HSV infections in mice and guinea-pigs when given either topically or by systemic administration by the subcutaneous, intravenous or oral routes. Comparisons of treatment with famciclovir and penciclovir demonstrated that the improved bioavailability of penciclovir following oral administration of famciclovir resulted in improved efficacy. In addition, there is good evidence to suggest that virus replication within the central nervous system is reduced following treatment with either penciclovir or famciclovir. The relative antiviral potencies in mouse cells and pharmacokinetic properties in mice suggested that acyclovir would be more efficacious than either penciclovir or famciclovir against HSV infections in mice. However, penciclovir and famciclovir in general were at least as effective as acyclovir against cutaneous, genital and intranasal infections. Moreover, in mice infected intraperitoneally with HSV-1, as with systemic administration of penciclovir, orally administered famciclovir, even when administered less frequently, was more active than equivalent treatment with acyclovir. This is consistent with the high stability of intracellular penciclovir-triphosphate within herpesvirus-infected cells and the prolonged activity of penciclovir in cell culture. The excellent pharmacokinetic properties of famciclovir in man coupled with the prolonged activity of penciclovir suggest that famciclovir will be effective in clinical use at both a lower dose and a reduced dosage frequency than acyclovir.