PHARMACOKINETICS OF FAMCICLOVIR IN MAN

This review presents briefly the results of a number of studies conducted in healthy volunteers, designed to investigate the pharmacokinetics of famciclovir, the oral form of the antiviral compound, penciclovir. These studies have shown that famciclovir is absorbed rapidly and extensively following oral administration. Extensive pre-systemic metabolism of famciclovir occurs since compound-related material in plasma consists almost entirely of deacetylated and oxidized metabolites. Little or no parent compound is detected in plasma or urine. The major metabolite of famciclovir is penciclovir. Maximum plasma concentrations of penciclovir are achieved rapidly following oral administration of famciclovir, and total systemic availability of penciclovir is high (77%). Pharmacokinetic parameters for penciclovir are linear over the famciclovir oral dose range 125-750 mg and the penciclovir intravenous dose range 10-20 mg kg-1. The distribution of penciclovir after intravenous administration is consistent with localization out of plasma and into tissues. Penciclovir is eliminated rapidly and almost unchanged by net active tubular secretion and glomerular filtration in the kidneys. The terminal phase elimination half-life of the compound in healthy subjects is approximately 2 h. A study in healthy elderly male subjects indicated no clinically significant effects of age on the pharmacokinetics of penciclovir following oral famciclovir administration. Food appears to slow the rate of availability of penciclovir from oral famciclovir, but has no effects on the extent of availability of penciclovir. These data indicate that famciclovir possesses excellent pharmacokinetic properties for the provision of clinically useful concentrations of the antiviral agent penciclovir in the oral treatment of herpesviral infections.