penciclovir and Chronic-Disease

Ducks congenitally infected with duck hepatitis B virus (DHBV) were treated with the antiviral guanine nucleoside analog penciclovir for 12 or 24 weeks at a dosage of 10 mg/kg of body weight per day. By the completion of both 12 and 24 weeks of therapy, molecular hybridization studies of the liver tissue revealed that the viral DNA, RNA, and protein levels were significantly reduced compared to those in the placebo-treated controls. Penciclovir treatment for 12 or 24 weeks was not associated with any toxicity, establishing the efficacy and safety of long-term penciclovir therapy in chronic DHBV infection.

Topics: Acyclovir; Animals; Antiviral Agents; Chronic Disease; DNA, Viral; Ducks; Guanine; Hepadnaviridae Infections; Hepatitis B Virus, Duck; Viral Proteins

Topics: Acyclovir; Animals; Antiviral Agents; Cells, Cultured; Chronic Disease; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Guanine; Hepatitis B; Hepatitis B Virus, Duck; Humans; Lamivudine; Liver; Virus Replication

The pharmacokinetic profile of penciclovir was determined after a single 500-mg dose of its oral precursor, famciclovir, in 9 healthy volunteers and in 14 patients with chronic hepatic disease. Plasma and urine samples were analyzed for concentrations of penciclovir and 6-deoxy-penciclovir using a reverse-phase high-performance liquid chromatography (HPLC) method. Famciclovir was not quantifiable in patients with hepatic disease, and 6-deoxy-penciclovir was quantifiable in only a limited number of specimens. The extent of systemic availability of penciclovir, as measured by AUC0-infinity, was similar in patients with hepatic disease and in healthy subjects. In contrast, Cmax was significantly lower (average decrease of 43%) in subjects with hepatic disease relative to healthy normal subjects. Median Tmax for subjects with hepatic disease was significantly increased (by 0.75 hours) compared with subjects with normal liver function. These data suggest a decrease in the rate, but not the extent, of systemic availability of penciclovir in patients with hepatic disease. It should be unnecessary to modify the dose of famciclovir for subjects with compensated hepatic disease and normal renal function.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Adolescent; Adult; Biological Availability; Chromatography, High Pressure Liquid; Chronic Disease; Famciclovir; Female; Guanine; Humans; Liver Diseases; Male; Metabolic Clearance Rate; Middle Aged; Prodrugs