Abstract
The species differences in renal tubular transport of uric acid are well known. Among various nonhuman mammalian species, rats belong to a group with a reabsorptive net flux of uric acid in the renal tubules, and hence they have sometimes been used to test uricosuric activity by a clearance technique. The stop-flow technique is also regarded as a useful method for evaluating drug effects on tubular transport of uric acid. This technique has been used with rabbits, dogs and cebus monkeys, but not with rats. Reported here is the utility of a stop-flow technique using rats. The fractional excretion value of uric acid (FEua) in rats with a high urine flow rate was nearly 1.0, which was clearly higher than those in clearance experiments. On the other hand, in pyrazinoic acid (PZO)-treated rats with inhibited secretion of uric acid, the FEua value was much lower than that in non-treated rats, and the stop-flow patterns always indicated a remarkable reabsorption of urate in the proximal tubules corresponding to the secretion of p-aminohippurate. As generally accepted, uricosuric drugs inhibit bidirectional transport of uric acid in the renal tubules. We describe the characteristics of uricosuric drugs using stop-flow techniques with PZO-treated and non-treated rats, and the uricosuric properties of a new uricosuric diuretic, S-8666, which has been developed in our laboratories.
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