PENCICLOVIR - A REVIEW OF ITS SPECTRUM OF ACTIVITY, SELECTIVITY, AND CROSS-RESISTANCE PATTERN

The antiherpesvirus agent penciclovir has been evaluated extensively i n cell culture. The spectrum of activity of penciclovir against human herpesviruses is similar to that of acyclovir, both compounds having g ood activity against herpes simplex viruses types 1 and 2 (HSV-1, HSV- 2), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Like a cyclovir, penciclovir has slight activity against cytomegalovirus (CMV ). The susceptibility of recent clinical isolates was not influenced b y geographical origin. The activity of penciclovir was examined in sev eral antiviral assays (plaque reduction, virus antigen, virus yield, a nd viral DNA inhibition) and in many different host cells (fibroblast, epithelial-like, keratinocyte). The comparative activity of penciclov ir and acyclovir depended on both the host cell and the assay and, whi le in certain circumstances penciclovir was more active than acyclovir , overall the activities of the two compounds were considered comparab le. 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 e xamined and, as expected, thymidine kinase-negative strains were resis tant to both penciclovir and acyclovir. The majority of acyclovir-resi stant 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 serie s of foscarnet-resistant HSV isolates appeared to be susceptible to bo th penciclovir and acyclovir. These results led to the evaluation of p enciclovir in further cell culture studies, and also in animal models. Furthermore, the mechanism of action of penciclovir has also been inv estigated. Since the oral absorption of penciclovir in animals was poo r, an oral form, famciclovir, was selected which gave improved oral bi oavailability of penciclovir.