A Simple Method for Estimating Drug-induced Hypreuricemia in Rats Treated with K-oxonate.

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A simple and practical method for estimating the character of drugs, which may clinically cause hyperuricemia, was devised using rats with a catheterized aorta loaded with an urate oxidase inhibitor, potassium oxonate. The method was so simple and economical for detecting the increase of plasma uric acid with drug administration that we could use it as a routine assay for investigating the characteristics of drugs with experimental animals. This report introduces the method together with some examples showing its utility. Potassium oxonate, administered i.p.at 250 mg/kg, effectively inhibited the action of urate oxidase for at least two hours, and prolonged inhibition of the enzyme was maintained by successive treatment with the agent every two hours. Under such conditions, we could easily detect an obvious increase of plasma uric acid upon treatment with some test drugs such as uric acid, isoproterenol, fructose, xylitol and diuretic antihypertensives. Potassium oxonate showed an apparent diuretic and hyperuricosuric action by itself, and hence the method could not be used to estimate the main action of uricosuric agents, while an obvious increase of plasma uric acid was also detected with a high dose of tienilic acid or probenecid.<BR>Of course, although we should further investigate whether the increase of plasma uric acid demonstrated by this method truly displays the character of drugs inducing clinical hyperuricemia, the simplicity of the method should greatly aid solving many problems concerning drug-induced hyperurlcemia.
Japanese Society of Gout and Nucleic Acid Metabolismの論文

A Simple Method for Estimating Drug-induced Hypreuricemia in Rats Treated with K-oxonate.

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