Lack of a pharmacokinetic interaction between oral famciclovir and allopurinol in healthy volunteers.
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 micrograms.ml-1, 8.8 micrograms.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 27 l.h-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 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 micrograms.ml-1, 5.73 micrograms.h.ml-1 and 1.38 h, respectively. Mean Cmax and AUC values of the active metabolite of allopurinol, oxypurinol were 11.2 micrograms.ml-1 and 96.0 micrograms.h.ml-1, respectively, and these were also unaltered by co-administration of famciclovir with allopurinol, with values of 10.6 micrograms/ml and 89.8 micrograms.h/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Fowles
S E
SE
Drug Metabolism and Pharmacokinetics Department, SmithKline Beecham Pharmaceuticals, Welwyn, Hertfordshire, UK.
Pratt
S K
SK
Laroche
J
J
Prince
W T
WT
D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000493:Allopurinol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D000077595:Famciclovir; D006147:Guanine; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010117:Oxypurinol / Q000008:administration & dosage / Q000493:pharmacokinetics
D000998:Antiviral Agents; C053539:penciclovir; D015075:2-Aminopurine; D006147:Guanine; D000493:Allopurinol; D010117:Oxypurinol; D000077595:Famciclovir; D000212:Acyclovir