| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Furosemide(FM), a loop diuretic, has been reported that the diuretic action of this drug is frequently decreased in patients with hepatic and renal dysfunction. However, the factors involved in this phenomenon have not been elucidated yet. Thus, in this study, we have investigated the pharmacokinetic-pharmacodynamic relationship of FM in rats and humans with hepatic or renal dysfunction.
A new evaluation method for diuretic response to FM was develop using the urinary excretion rate of (Na+K) as an index of diuresis. In view of the action mechanism of FM, this index was more reliable than the urinary excretion rate of Na.
In the drug excretion-response curve, apparent sensitivity to FM was lower in the rat with aute hepatic failure(AHF) than in normal rat. On the other hand, it was higher in the rat with aute renal failure(ARF) than normal rat. The altered function at distal parts of the nephron was suggested by the change of reabsorption of water and ions in these rats. This alteration of reabsorption may be related with the change of endocrine system, especially with the plasma concentration of aldosterone.
In the isolated perfused kidney, which was indepandent from endocrine system, the increased sensitivity to FM was also observed in ARF rats. Therfore, interarenal factors also affected to the response in renal disease.
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