Penciclovir: a review of its spectrum of activity, selectivity, and cross-resistance pattern

The antiherpesvirus agent penciclovir has been evaluated extensively in cell culture. The spectrum of activity of penciclovir against human herpesviruses is similar to that of acyclovir, both compounds having good activity against herpes simplex viruses types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Like acyclovir, penciclovir has slight activity against cytomegalovirus (CMV). The susceptibility of recent clinical isolates was not influenced by geographical origin. The activity of penciclovir was examined in several antiviral assays (plaque reduction, virus antigen, virus yield, and viral DNA inhibition) and in many different host cells (fibroblast, epithelial-like, keratinocyte). The comparative activity of penciclovir and acyclovir depended on both the host cell and the assay and, while in certain circumstances penciclovir was more active than acyclovir, overall the activities of the two compounds were considered comparable. Both compounds were highly selective antiviral agents with minimal effects on a wide range of representative, proliferating human cells. The inhibition of a variety of acyclovir-resistant strains has been examined and, as expected, thymidine kinase-negative strains were resistant to both penciclovir and acyclovir. The majority of acyclovir-resistant HSV and VZV clinical strains were cross-resistant to penciclovir. However, certain acyclovir-resistant strains, some of which were of clinical origin and all of which expressed altered thymidine kinase or DNA polymerase, were susceptible to penciclovir. In addition, a series of foscarnet-resistant HSV isolates appeared to be susceptible to both penciclovir and acyclovir. These results led to the evaluation of penciclovir in further cell culture studies, and also in animal models. Furthermore, the mechanism of action of penciclovir has also been investigated. Since the oral absorption of penciclovir in animals was poor, an oral form, famciclovir, was selected which gave improved oral bioavailability of penciclovir.