The tolerance to and pharmacokinetics of penciclovir (BRL 39,123A), a novel antiherpes agent, administered by intravenous infusion to healthy subjects.

The tolerance to and pharmacokinetics of intravenously administered penciclovir (BRL 39,123A), a novel anti-herpes agent, were investigated in 15 healthy male subjects. The volunteers were divided into three groups, receiving either 10, 15 or 20 mg/kg penciclovir by a 60 min constant-rate infusion. Blood samples were taken sequentially up to 48 h after the start of the infusion and urine collections made at appropriate intervals up to 72 h. After a simple solid phase extraction, concentrations of penciclovir in plasma and urine were determined using HPLC with U.V. detection. Mean values of Cmax, corresponding usually with the end of infusion, and of AUC appeared to increase proportionately with dose. Furthermore, there was no evidence that dose significantly affected any individual pharmacokinetic parameter. Penciclovir was distributed into tissues with an overall mean volume of distribution of approximately 1.5 l.kg-1, i.e. approximately double that of body water. It was rapidly eliminated, with a mean total plasma clearance of 39.3 l.h-1, and a mean terminal-phase half-life of 2.0 h. The majority of the dose, approximately 70%, was excreted unchanged in the urine. Mean renal clearance of BRL 39,123 was 28.1 l.h-1, which exceeds normal glomerular filtration rate and approaches renal plasma flow. At all dose-levels, the infusions of penciclovir were well tolerated, with no evidence of drug-related adverse events.