大鼠体内14C-呋塞米的药代动力学、胆汁排泄及代谢研究。

Pharmacokinetic, biliary excretion, and metabolic studies of 14C-furosemide in the rat.

Prandota J, Pruitt A W

J. Korczak Memorial Children's Hospital, Wrocław, Poland.

Xenobiotica. 1991 Jun;21(6):725-36. doi: 10.3109/00498259109039512.

Abstract

Partition of furosemide into organic solvents at pH 3.8 was greatest for ethyl acetate (33:1) greater than 2-ethyl-1-hexanol (10:1) greater than ethyl ether (6:1). 2. Furosemide was highly bound to human, bovine, rabbit, and rat plasma or albumin (97.4-98.4%). 3. Furosemide was highly bound to rat tissues. One hour after i.p. injection of the drug, tissue to plasma concentration ratios were: adrenals (10:1), lung (4:1), kidney (4:1), spleen (3:1). 4. In rats with ligated renal pedicles, furosemide was excreted in bile, at least in part, by active transport. Hepatic clearance of a 1 mg/kg i.v. dose contributed 20% to total body clearance. Large doses (50 mg/kg and more) of furosemide exerted a choleretic effect. 5. Chromatography of bile showed that i.v. administration of 50 mg/kg and higher doses of furosemide to rats resulted in saturation of hepatic drug metabolism. 6. The bile of rats contained the parent drug, 4-chloro-5-sulphamoyl-anthranilic acid, and at least two unknown metabolites with the furan ring intact.

摘要

在pH 3.8条件下，呋塞米在有机溶剂中的分配情况为：乙酸乙酯（33:1）大于2-乙基-1-己醇（10:1）大于乙醚（6:1）。2. 呋塞米与人、牛、兔和大鼠的血浆或白蛋白高度结合（97.4 - 98.4%）。3. 呋塞米与大鼠组织高度结合。腹腔注射该药物1小时后，组织与血浆浓度比为：肾上腺（10:1）、肺（4:1）、肾（4:1）、脾（3:1）。4. 在肾蒂结扎的大鼠中，呋塞米至少部分通过主动转运经胆汁排泄。静脉注射1 mg/kg剂量时，肝脏清除率占全身清除率的20%。大剂量（50 mg/kg及以上）的呋塞米具有利胆作用。5. 胆汁色谱分析表明，对大鼠静脉注射50 mg/kg及更高剂量的呋塞米会导致肝脏药物代谢饱和。6. 大鼠胆汁中含有母体药物、4-氯-5-氨磺酰基-邻氨基苯甲酸以及至少两种呋喃环完整的未知代谢物。