Uricosuric and diuretic activities of DR-3438 in dogs and rabbits.
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- TANAKA Satoru
- Research Institute, Daiichi Pharmaceutical Co., Ltd.
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- KANDA Akira
- Research Institute, Daiichi Pharmaceutical Co., Ltd.
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- ASHIDA Shin-ichiro
- Research Institute, Daiichi Pharmaceutical Co., Ltd.
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抄録
The purpose of this study was to evaluate the uricosuric and diuretic properties of the new diuretic agent DR-3438. In the conventional clearance studies in urate-loaded dogs, intravenous injection of DR-3438 (3-30 mg/kg) resulted in dose-related increases in fractional excretion of urate (FEua), urine flow and sodium excretion. At doses causing similar natriuresis, tienilic acid (50 mg/kg, i.v.) markedly increased the FEua value, whereas indacrinone (1 mg/kg, i.v.) had no significant effect on it. Trichloromethiazide (1 mg/kg, i.v.) and furosemide (0.3 mg/kg, i.v.) tended to decrease the FEua. Thus, the uricosuric activity of DR-3438 (30 mg/kg) was 0.6-fold that of tienilic acid and 3.4-fold that of indacrinone. In contrast, in urate-loaded rabbits that exhibit net tubular secretion of urate, intravenous DR-3438 (30 mg/kg) produced a significant decrease in FEua. Stop-flow studies in dogs revealed that DR-3438 (30 mg/kg) blocks both urate reabsorption and p-aminohippurate secretion in the proximal segment of the nephron and strongly inhibits reabsorption of water, sodium and potassium in the distal segments. These results suggest that DR-3438 exerts uricosuric activity through blocking urate transport in the proximal tubules and diuretic and saluretic activities by inhibiting water and sodium reabsorption in the distal segment of the nephron.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 54 (3), 307-314, 1990
公益社団法人 日本薬理学会