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  • Title: Absorption and disposition of furosemide in healthy volunteers, measured with a metabolite-specific assay.
    Author: Smith DE, Lin ET, Benet LZ.
    Journal: Drug Metab Dispos; 1980; 8(5):337-42. PubMed ID: 6107232.
    Abstract:
    The objectives of this study were to qualitatively and quantitatively compare the metabolism, pharmacokinetics, and bioavailability of furosemide in healthy volunteers after intravenous and oral administration. We also determined the plasma protein binding of furosemide in vivo after iv administration. Nine males received furosemide (Hoechst, 40 mg iv and 80 mg po) in a random crossover fashion. Serial plasma samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced throughout the study. Furosemide as well as its potential metabolites were measured by a rapid, sensitive, and specific spectrofluorimetric HPLC assay. Total plasma clearance averaged 164 +/- 26 (SD) ml/min, of which 66.2 +/- 6.8% represented renal clearance of unchanged drug. Volume of distribution (steady-state) was 109 +/- 19 ml/kg. These clearance and volume measurements are in good agreement with data previously published by our group. The mean absolute bioavailability of furosemide was 42.8 and 44.0%, as calculated from plasma and urine data, respectively. Protein binding of furosemide in vivo was determined by a spectrofluorimetric HPLC assay and ranged from 98.5 to 99.1%. Approximately 5.5 mg of furosemide was excreted as a glucuronide conjugate after iv dosing and about 5.1 mg after po administration. We found no evidence of the proposed metabolite of furosemide, 2-amino-4-chloro-5-sulfamoylanthranilic acid (CSA) in any of our plasma or urine samples. In addition, we conclusively demonstrated CSA to be an analytical artifact.
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