Linear pharmacokinetics of penciclovir following administration of single oral doses of famciclovir 125, 250, 500 and 750 mg to healthy volunteers.

Author(s): Pue MA, Pratt SK, Fairless AJ, Fowles S, Laroche J, Georgiou P, Prince W

Affiliation(s): SmithKline Beecham Pharmaceuticals, Welwyn, Herts, UK.

Publication date & source: 1994-01, J Antimicrob Chemother., 33(1):119-27.

Publication type: Clinical Trial; Randomized Controlled Trial

Twenty healthy male volunteers received single oral doses of famciclovir (125-750 mg), in a randomized, single-blind, crossover study. Plasma and urine concentrations of penciclovir and its 6-deoxy precursor, BRL 42359, were determined and penciclovir plasma concentration-time data submitted to model-independent pharmacokinetic analysis. Peak plasma concentrations of penciclovir were obtained at median times of 0.5-0.75 h after dosing. The areas under the concentration versus time curves (AUC) and the peak penciclovir concentration (Cmax) increased linearly with dose of famciclovir. Time to Cmax, elimination half-life, urinary recovery and renal clearance of penciclovir did not change with increasing dose. Famciclovir was excreted via the kidneys as penciclovir (60%) and BRL 42359 (5%), respectively. Famciclovir was well tolerated by all subjects with a low incidence of adverse effects. In conclusion, penciclovir thus displays linear pharmacokinetics in the anticipated therapeutic dose range of famciclovir.