LACK OF A PHARMACOKINETIC INTERACTION BETWEEN ORAL FAMCICLOVIR AND ALLOPURINOL IN HEALTHY-VOLUNTEERS

Famciclovir has been shown to have potent and selective activity again st herpesviruses. The possibility of a pharmacokinetic interaction bet ween the anti-viral agent, famciclovir and allopurinol has been invest igated in twelve healthy male volunteers following a single oral dose of famciclovir (500 mg) in the presence and absence of steady-state le vels 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-phas e half-life for penciclovir following administration of famciclovir al one at 3.3 mu g.ml(-1), 8.8 mu g.h.ml(-1) and 2.1 h, respectively were unchanged by co-administration of allopurinol. Similarly, mean urinar y recovery and renal clearance values of penciclovir following famcicl ovir alone were 56.8% and 27 lh(-1) and when given with allopurinol 59 .7% and 27.5 l.h(-1), respectively. No evidence of accumulation of the inactive precursor to penciclovir, BRL 42359, was noted as a result o f co-administration of the two drugs. Mean steady-state C-max, AUC and terminal-phase half-life values for allopurinol after co-administrati on of allopurinol with famciclovir also appeared unchanged from values obtained after dosing of allopurinol alone, at 2.12 mu g.ml(-1), 5.73 mu g.h.ml(-1) and 1.38h, respectively. Mean C-max and AUCvalues of th e active metabolite of allopurinol, oxypurinol were 11.2 mu g ml(-1) a nd 96.0 mu g.h.ml(-1), respectively, and these were also unaltered by co-administration of famciclovir with allopurinol, with values of 10.6 mu g/ml and 89.8 mu g.h.ml(-1), respectively. In summary, no evidence of a pharmacokinetic interaction between allopurinol and famciclovir was observed when the two drugs were given concomitantly to healthy vo lunteers.