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.
Prandota
J
J
J. Korczak Memorial Children's Hospital, Wrocław, Poland.
Pruitt
A W
AW
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D005665:Furosemide / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D012709:Serum Albumin; D005665:Furosemide