title: Linear pharmacokinetics of penciclovir following administration of single oral doses of famciclovir 125, 250, 500 and 750 mg to healthy volunteers.
abstract: 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.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Welwyn, Herts, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Pue
authors.forename: S K
authors.initials: SK
authors.lastname: Pratt
authors.forename: A J
authors.initials: AJ
authors.lastname: Fairless
authors.forename: S
authors.initials: S
authors.lastname: Fowles
authors.forename: J
authors.initials: J
authors.lastname: Laroche
authors.forename: P
authors.initials: P
authors.lastname: Georgiou
authors.forename: W
authors.initials: W
authors.lastname: Prince
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000212:Acyclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D000077595:Famciclovir; D006147:Guanine; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000998:Antiviral Agents; D011355:Prodrugs; C080051:BRL 42359; C053539:penciclovir; D015075:2-Aminopurine; D006147:Guanine; D000077595:Famciclovir; D000212:Acyclovir