PHARMACOKINETICS OF FAMCICLOVIR IN SUBJECTS WITH CHRONIC HEPATIC-DISEASE

The pharmacokinetic profile of penciclovir was determined after a sing le 500-mg dose of its oral precursor, famciclovir, in 9 healthy volunt eers and in 14 patients with chronic hepatic disease. Plasma and urine samples were analyzed for concentrations of penciclovir and 6-deoxy-p enciclovir using a reverse-phase high-performance liquid chromatograph y (HPLC) method. Famciclovir was not quantifiable in patients with hep atic disease, and 6-deoxy-penciclovir was quantifiable in only a limit ed number of specimens. The extent of systemic availability of pencicl ovir, as measured by AUC(0-infinity) , was similar in patients with he patic disease and in healthy subjects. In contrast, C-max was signific antly lower (average decrease of 43%) in subjects with hepatic disease relative to healthy normal subjects. Median T-max for subjects with h epatic disease was significantly increased (by 0.75 hours) compared wi th subjects with normal liver Junction. These data suggest a decrease in the rate, but not the extent, of systemic availability of penciclov ir in patients with hepatic disease. It should be unnecessary to modif y the dose of famciclovir for subjects with compensated hepatic diseas e and normal renal function,