Uricosuric property of a new diuretic compound, S‐8666‐S‐(‐)‐enantiomer in rats

Abstract

AbstractThe uricosuric property of S‐8666‐S‐(‐)‐enantiomer (S), which is the diuretic component of the uricosuric diuretic agent S‐8666, was studied using rats. S markedly increased the tubular fractional excretion of uric acid in a stop‐flow analysis using rats treated with pyrazinoic acid (PZO), an inhibitor of tubular urate secretion, but did not affect the tubular urate transport in animals not treated with PZO. On the other hand, S was hypouricosuric and hyperuricemic in a clearance study using rats treated with oxonate, a uricase inhibitor, and also in an experiment using eviscerated rats with functional hepatectomy. The diuretic property of S was comparable to that of furosemide in rats. However, furosemide under an equivalent diuretic response was more potently hypouricosuric in oxonate‐treated rats and eviscerated rats with functional hepatectomy and even in the stop‐flow experiments, and more hyperuricemic in eviscerated rats with functional hepatectomy. The hypouricosuric effect of S in oxonate‐treated rats could be canceled by administration together with the R‐(+)‐enantiomer. These results led to the conclusion that S is less hypouricosuric and hyperuricemic than furosemide at an equivalent diuretic dose owing to its dual effects on tubular urate transport, and the hypouricosuric property can be canceled by administration together with the R‐(+)‐enantiomer.