A study of dose-response relationships of allopurinol in the presence of low or high purine turnover.
Effects of allopurinol (125-500 mg/m2 body surface) were studied in normal subjects during periods of 18 days both during a purine-free, isoenergetic liquid formula diet and additional intake of ribonucleic acid, 4 g/day. Plasma uric acid and renal excretion of uric acid, oxypurines (hypoxanthine plus xanthine) and orotic acid were measured and total purine excretion calculated. Effects of allopurinol were evaluated by comparison of the results obtained in the steady state during diet alone (average of days 7-10) with those during allopurinol administration (days 16-18). During the purine-free diet, plasma uric acid was lowered more than urinary uric acid by allopurinol on doses of 250-500 mg/m2 (44%-54% of control values on 500 mg/m2), demonstrating an increase in renal clearance. At the same dose, the uric acid lowering effect of allopurinol was more pronounced with than without purine loads (plasma 41%, urine 32% of control on 500 mg/m2 during purine intake), while renal uric acid clearance was decreased. The more pronounced reduction of uric acid excretion during purine administration was balanced to the greater part by a more pronounced increase in oxypurine excretion. Total purine excretion was reduced by about 20% during the purine-free diet irrespective of dose. The size of this purine deficit was doubled, but was also independent of dose during addition of purines. Orotic acid excretion increased with dose during allopurinol treatment and was reduced by addition of purines.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000493:Allopurinol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D011687:Purines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012313:RNA / Q000008:administration & dosage; D014527:Uric Acid / Q000652:urine
D011687:Purines; D014527:Uric Acid; D012313:RNA; D000493:Allopurinol