抄録
イヌにフロセミド(5mg/Kg)を静脈内投与した後の血漿中動態, 利尿効果, 尿中並びに胆汁中排泄に対する実験的腎不全の影響について検討した. 正常犬にフロセミドを投与すると著しい利尿効果が発現し, 6時間目までに尿と胆汁中にそれぞれ投与量の約55%並びに約45%が排泄された. 50%利尿効果は血漿中濃度1.5μg/ml, 尿中排泄速度約100μg/minのとき得られた. 塩化第二水銀(2mg/kg)の静脈内投与により作製した腎不全犬において, フロセミドの利尿効果の低下と共に生物学的半減期の延長と腎クリアランスの著しい減少が観察された. 一方, 胆汁中排泄はほとんど影響受けなかった. また, 利尿効果と血漿中フロセミド濃度との関係は大きく右方に移動したが, フロセミドの尿中排泄速度との関係はほとんど変化しなかった. 以上のことより, 腎不全犬におけるフロセミドの利尿効果の低下は, フロセミドの尿細管に対する感受性の低下によるものではなく主に腎排泄量の低下に起因することが示唆された.
The pharmacokinetics and the biliary and urinary excretions following intravenous administration of furosemide (5 mg/kg) were investigated in the anesthetized dogs with normal and experimentally reduced renal function. After the administration, furosemide caused diuretic and choleretic response, and was excreted into urine and bile at almost similar rate to plasma concentration decay in normal dogs. Half maximum diuretic response was obtained at 1.5μg/ml of plasma concentration and 100μg/min of urinary excretion rate of furosemide. Acute renal failure was produced in dogs by the intravenous administration of mercuric chloride (HgCl_2, 2mg/kg). In HgCl_2-treated dogs, the prolongation of half life (T_<1/2>β) and the decrease in plasma clearance were noted with the decreased diuretic response. These changes in parameters appeared to be associated with the decrease in excretion of furosemide into the urine, but not into the bile. Plasma level-diuretic response relationship was extensively shifted to the right in HgCl_2-treated dogs, while urinary dose-response relationship did not change significantly between two groups. These results suggest that the decreased response to furosemide in HgCl_2-treated dogs seems to be due to the decreased renal clearance rather than to the subsensitivity to furosemide on the site of action.
