Clinical Pharmacology & Therapeutics · 1979 · 102 citations · 0 references
PharmacyPharmacokineticsPharmacologyDrug ClearanceDrug MetabolismMetabolismCytochrome P450-mediated MetabolismDrug DispositionDrug-metabolizing EnzymesMetabolic ClearanceMultiple-dose PharmacokineticsXenobiotic MetabolismBiotransformationMultiple Dosing ModelsRenal Plasma ClearanceTheophylline TherapyUric Acid MetabolismXanthine Oxidoreductase Metabolism
The effects of allopurinol on the plasma clearance and metabolism of theophylline in man were investigated under single-dose and multiple-dosing conditions. No change in theophylline clearance was found with the concomitant use of allopurinol but 1-methylxanthine (1MX), a theophylline metabolite not previously described in man, was detected in urine during control and allopurinol treatment phases under both single- and multiple-dosing conditions. 1MX excretion increased at the expense of 1-methyluric acid (1MU) during the allopurinol treatment phase. It is proposed that the secondary biotransformation of 1MX to 1MU is mediated by xanthine oxidase.