[Effect of metronidazole on phenazone metabolism]

Nine volunteers received in random order on three occasions either 15 mg/kg phenazone (antipyrine; in the following called phenazone, INN), 15 mg/kg phenazone and 1000 mg cimetidine or 15 mg/kg phenazone and 1000 mg metronidazole. Cimetidine prolonged phenazone half-life from 12.7 +/- 1.0 h to 15.5 +/- 1.0 h (p less than 0.05) and decreased total plasma clearance of phenazone from 40.9 +/- 3.9 ml/min to 33.9 +/- 2.9 ml/min (p less than 0.05). When metronidazole was given with phenazone to the volunteers no change of phenazone pharmacokinetics in plasma occurred. Urinary excretion of the main oxidative metabolites of phenazone (4-hydroxyphenazone, 3-hydroxymethylphenazone and norphenazone) was unaffected during cimetidine as well as metronidazole treatment. Both metronidazole and cimetidine potentiate the anticoagulant effect of warfarin. In contrast it could be shown that cimetidine does not interact with the metabolism of phenprocoumon. Whether metronidazole interferes with the pharmacokinetics of phenprocoumon should be studied in further investigations.