Intraocular and plasmatic pharmacokinetics of penciclovir in human after a single oral dose

Abstract

Abstract: : Purpose:To develop a population pharmacokinetic (Pk) model for penciclovir (PCV) in human eye and plasma after oral administration of 500mg of famciclovir (FCV). Methods:The population approach was used (implemented with NONMEM) to analyse PCV Pk data in humour aqueous and plasma from 31 patients undergoing cataract surgery. Patients received 500mg of FCV at various times (between 2 and 12 hours) before the surgery. The concentrations of PCV in both blood and aqueous humour were assayed by high–performance liquid chromatography coupled with a fluorescence detector. Results:Pk data followed a two–compartment model. Population and individual Pk parameters were determined for plasma and aqueous humour. At 2, 4 and 6 hours, the ratios of the predicted concentrations in aqueous to the concentrations in plasma were 14%, 28% and 39%, respectively. The mean elimination half–life from plasma and aqueous humour was 3.0 hours, with 26% interindividual variability. In aqueous humour, the predicted Cmax and Tmax were 0.72 µg/ml and 3.58 hours, respectively. Mean aqueous humour clearance and Vd were estimated at 1.17 µl/min and 200 µl, respectively. Plasmatic clearance and Vd were ranged between 8.5–38.2 l/h and 52–129 l, respectively. Conclusions:The selected population Pk model accurately characterised PCV PK in both aqueous humour and plasma and allowed to calculate Pk parameters. After one 500mg dose of FCV, predicted maximal concentrations of PCV in the eye were above the in vitro IC50.

Keywords: antiviral drugs • pharmacology • varicella zoster virus