Effect of drugs on urate binding to plasma proteins.
The effect of various drugs on urate binding to plasma proteins was investigated in normal subjects. Whereas allopurinol, aspirin, phenylbutazone, probenecid, and sulphinpyrazone all significantly reduced plasma urate concentrations, only aspirin, phenylbutazone, and probenecid significantly impaired urate binding. Colchicine and indomethacin in the doses administered had no significant effect on plasma urate concentrations or binding. In the case of aspirin, urate binding was reduced to 25% of normal, and this effect was quickly abolished after cessation of therapy. Phenylbutazone reduced urate binding to 56% and probenecid to 46% of normal; this impairment was still detected four days after cessation of therapy. Drugs may impair urate binding by competition for plasma protein binding sites, with displacement of bound urate. Impairment of urate binding in vivo by administration of certain drugs may be relevant to the precipitation of acute gouty arthritis, to the formation of gouty tophi, and to the augmentation of uricosuria. Furthermore, the role of drugs must be seriously considered during all studies on urate binding in patients with gout.
D000328:Adult; D000493:Allopurinol / Q000494:pharmacology; D001168:Arthritis / Q000139:chemically induced; D001241:Aspirin / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D002848:Chromatography, DEAE-Cellulose; D003078:Colchicine / Q000494:pharmacology; D005260:Female; D006073:Gout / Q000139:chemically induced; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010653:Phenylbutazone / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects*; D013442:Sulfinpyrazone / Q000494:pharmacology; D014527:Uric Acid / Q000378:metabolism*
D001798:Blood Proteins; D014527:Uric Acid; D000493:Allopurinol; D010653:Phenylbutazone; D011339:Probenecid; D001241:Aspirin; D003078:Colchicine; D013442:Sulfinpyrazone; D007213:Indomethacin