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

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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 Cmax, 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 Cmax, 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 Cmax 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.