Uricosuric Activity in Relevant Animal Models

Most species have low plasma levels and low renal excretion of uric acid and thus are poor models for the human. There are two exceptions, however the Dalmatian dog and the Cebus monkey. 

The Dalmatian dog has excessive uric acid excretion and relatively high plasma levels. This is due to a genetically determined defect in tubular reabsorption of filtered urate (Friedman and Byers 1948 Kessler et al. 1959) and defective hepatic uricase activity (Yii et al. 1971). The Dalmatian dog can therefore being used for studies of uricosuric agents. 

The Cebus monkey is described not to possess uricase (Simkin 1971) and to have different metabolic conditions for uric acid than other experimental animals. This species is chosen for special studies of anti-uricopathic drugs since it resembles more closely human uric acid metabolism. 

Fasted Cebus monkeys (Cebus albifrons) of either sex weighing 3.0 to 5.0 kg are used. On the morning of the experiment, the animals receive 20 ml/kg drinking water by gavage, followed by oral administration of the test compound. Allopurinol and probenecid are used as control compounds. Control animals receive water only. The animals are placed in individual metabolism cages and the spontaneously voided urine is collected after 2, 6, and 24 h. After 2 and 6 h, an additional 4 ml/kg water is given by gavage. From a cubital vein blood is withdrawn prior to the experiment and 2, 6 and 24 h after application. 

Urine and serum samples are analyzed for uric acid (Uricaquant-method), creatinine (Jaffe reaction), sodium and potassium (flame photometry), calcium and magnesium (atom absorption method), and chloride (argentometry) as well as for osmolality. 

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