PENCICLOVIR PHARMACOKINETICS AND DISTRIBUTION TO THE BRAIN AND MUSCLEOF RATS, STUDIED BY MICRODIALYSIS

Famciclovir, the oral form of penciclovir, is a potent, highly selecti ve antiherpesvirus agent licenced For the treatment of herpes tester ( shingles). Some herpesviruses are prone to infect the central nervous system. To obtain guidance for the possible treatment of herpes enceph alitis it is important to study the extent of transport of antiviral a gents 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 a dministration. The AUC (area under the time versus concentration curve ) (0-5 h) of penciclovir in the brain was 0.096+/-0.018 (mean+/-SEM) o f the AUC in muscle while the mean ratio of brain to muscle concentrat ion 5 h post-injection was 0.180+/-0.084. Famciclovir given per os to rat at a dose of 120 mg kg(-1) resulted in a concentration ratio for p enciclovir between brain and muscle of 0.415+/-0.078 at 5 h after admi nistration, while the AUC ratio (0-5 h) was 0.143+/-0.012. Both of the se are higher than after i.v. injection of penciclovir. Penciclovir an d famciclovir were also administrated by i.v. infusion (60 and 80 mg k g(-1) h(-1) respectively). Famciclovir administration (AUG 0.075+/-0.0 25 mmol h L-1) did not increase penciclovir transport to the brain com pared with penciclovir administration (AUG 0.163+/-0.018 mmol h L-1).