ISSN:
1432-1440
Keywords:
Allopurinol
;
Uric acid
;
Oxypurines
;
Orotic acid
;
Dietary purines
;
Overproduction
;
Purine deficit
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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 increased 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. With respect to uric acid lowering effects, these results are in accordance with findings in patients overproducing uric acid endogenously and suggest that the uric acid lowering effect of allopurinol is enhanced with increasing concentrations of purine bases, presumably due to the tight binding of oxipurinol to xanthine oxidase. The small uricosuric effect of allopurinol seen during ingestion of the purine-free diet possibly is attributable to drug-induced orotic aciduria. The increase in size during purine intake of the purine deficit may result from reduced absorption of dietary purines during allopurinol treatment. Apparently, maximum effects of allopurinol on endogenous synthesis and/or absorption of purines from the gut are exerted by low doses.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01727784
