The clinical pharmacokinetics of famciclovir

Famciclovir is an oral prodrug of the antiherpesvirus nucleoside analogue, penciclovir. Following oral administration famciclovir undergoes extensive first pass metabolism to penciclovir and essentially no parent compound is recovered from plasma or urine. Penciclovir plasma concentrations reach a maximum less than 1 hour after famciclovir administration in fasting individuals, but are delayed if famciclovir is taken within 2 hours of a meal. The bioavailability of penciclovir, measured by urinary recovery, is approximately 60% and is not affected by food. Over the likely therapeutic dose range of famciclovir 125 mg to 750 mg, the pharmacokinetics of penciclovir are linear. The volume of distribution of penciclovir after intravenous administration is more than 1 L/kg, indicating extensive distribution into the tissue. Penciclovir is predominantly eliminated unchanged by the kidney, partly by active tubular excretion and has a terminal phase elimination half-life (t1/2 beta) of between 2 and 2.5 hours and a renal clearance (CLR) of between 25 and 30 L/h in individuals with normal renal function. In those with severe renal impairment the CLR falls markedly and the t1/2 beta increases to over 18 hours. Haemodialysis appears to be effective in clearing penciclovir from plasma. Elderly individuals tolerate famciclovir well, despite slower elimination secondary to age-related lower renal clearance. Uncomplicated herpes zoster does not affect the pharmacokinetic profile of penciclovir. In the limited studies undertaken so far, no significant drug interactions have been demonstrated.