Lack of a pharmacokinetic interaction between oral famciclovir and allopurinol in healthy volunteers

Abstract

Famciclovir has been shown to have potent and selective activity against herpesviruses. The possibility of a pharmacokinetic interaction between the anti-viral agent, famciclovir and allopurinol has been investigated in twelve healthy male volunteers following a single oral dose of famciclovir (500 mg) in the presence and absence of steady-state levels of allopurinol (300 mg). Similarly, the pharmacokinetic profiles of allopurinol and oxypurinol prior to and following a single dose of famciclovir were compared.

Mean values of C_max, AUC and terminal-phase half-life for penciclovir following administration of famciclovir alone at 3.3 μg·ml^-1, 8.8 μ·h·ml^-1 and 2.1 h, respectively were unchanged by co-administration of allopurinol. Similarly, mean urinary recovery and renal clearance values of penciclovir following famciclovir alone were 56.8% and 271·h^-1, and when given with allopurinol 59.7% and 27.51·h^-1, respectively. No evidence of accumulation of the inactive precursor to penciclovir, BRL 42359, was noted as a result of co-administration of the two drugs.

Mean steady-state C_max, AUC and terminal-phase half-life values for allopurinol after co-administration of allopurinol with famciclovir also appeared unchanged from values obtained after dosing of allopurinol alone, at 2.12 μg·ml^-1, 5.73 μg·h·ml^-1 and 1.38h, respectively. Mean C_max and AUC values of the active metabolite of allopurinol, oxypurinol were 11.2 μg·ml^-1 and 96.0 μg·h·ml^-1, respectively, and these were also unaltered by co-administration of famciclovir with allopurinol, with values of 10.6 μg/ml and 89.8 μg·h/ml, respectively.

In summary, no evidence of a pharmacokinetic interaction between allopurinol and famciclovir was observed when the two drugs were given concomitantly to healthy volunteers.