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

1. 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.