PHARMACOKINETICS OF FAMCICLOVIR IN MAN

This review presents briefly the results of a number of studies conduc ted in healthy volunteers, designed to investigate the pharmacokinetic s of famciclovir, the oral form of the antiviral compound, penciclovir . These studies have shown that famciclovir is absorbed rapidly and ex tensively following oral administration. Extensive pre-systemic metabo lism of famciclovir occurs since compound-related material in plasma c onsists almost entirely of deacetylated and oxidized metabolites. Litt le or no parent compound is detected in plasma or urine. The major met abolite of famciclovir is penciclovir. Maximum plasma concentrations o f penciclovir are achieved rapidly following oral administration of fa mciclovir, and total systemic availability of penciclovir is high (77% ). Pharmacokinetic parameters for penciclovir are linear over the famc iclovir oral dose range 125-750 mg and the penciclovir intravenous dos e range 10-20 mg kg-1. The distribution of penciclovir after intraveno us administration is consistent with localization out of plasma and in to 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 s ubjects is approximately 2 h. A study in healthy elderly male subjects indicated no clinically significant effects of age on the pharmacokin etics of penciclovir following oral famciclovir administration. Food a ppears to slow the rate of availability of penciclovir from oral famci clovir, but has no effects on the extent of availability of penciclovi r. These data indicate that famciclovir possesses excellent pharmacoki netic properties for the provision of clinically useful concentrations of the antiviral agent penciclovir in the oral treatment of herpesvir al infections.