Penciclovir Pharmacokinetics and Distribution to the Brain and Muscle of Rats,Studied by Microdialysis

Abstract

Famciclovir, the oral form of penciclovir, is a potent, highly selective antiherpesvirus agent licenced for the treatment of herpes zoster (shingles). Some herpesviruses are prone to infect the central nervous system. To obtain guidance for the possible treatment of herpes encephalitis it is important to study the extent of transport of antiviral agents into the brain. We have used microdialysis to sample the unbound extracellular concentration of penciclovir in the gastrocnemic muscle (which corresponds directly to plasma free concentrations) and in the brain of rats under halothane anaesthesia. Penciclovir (50 mg kg⁻¹) was given intravenously (i.v.) and samples were taken for 5 h after administration. The AUC (area under the time versus concentration curve) (0–5 h) of penciclovir in the brain was 0.096±0.018 (mean±SEM) of the AUC in muscle while the mean ratio of brain to muscle concentration 5 h post-injection was 0.1 80±0.084. Famciclovir given per os to rat at a dose of 1 20 mg kg⁻¹ resulted in a concentration ratio for penciclovir between brain and muscle of 0.415±0.078 at 5 h after administration, while the AUC ratio (0–5 h) was 0.143±0.012. Both of these are higher than after i.v. injection of penciclovir. Penciclovir and famciclovir were also administrated by i.v. infusion (60 and 80 mg kg⁻¹ h⁻¹ respectively). Famciclovir administration (AUC 0.075±0.025 mmol h L⁻¹) did not increase penciclovir transport to the brain compared with penciclovir administration (AUC 0.163±0.018 mmol h L⁻¹).