ABSORPTION AND DISPOSITION OF FUROSEMIDE IN HEALTHY-VOLUNTEERS, MEASURED WITH A METABOLITE-SPECIFIC ASSAY

  • 1 January 1980
    • journal article
    • research article
    • Vol. 8  (5) , 337-342
Abstract
The objectives of this study were to compare qualitatively and quantitatively the metabolism, pharmacokinetics and bioavailability of furosemide in healthy volunteers after i.v. and oral [i.p.] administration. The plasma protein binding of furosemide was determined in vivo after i.v. administration. Nine males received furosemide (Hoechst, 40 mg i.v. and 80 mg p.o.) in a random crossover fashion. Serial plasma samples were collected over 24 h. Fluid and electrolyte urinary losses were replaced throughout the study. Furosemide and its potential metabolites were measured by a rapid, sensitive and specific spectrofluorimetric HPLC [high performance liquid chromatography] 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. The clearance and volume measurements are in good agreement with data previously published. 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 98.5-99.1%. Furosemide .apprx. 5.5 mg was excreted as a glucuronide conjugate after i.v. dosing and .apprx. 5.1 mg after p.o. administration. No evidence of the proposed metabolite of furosemide, 2-amino-4-chloro-5-sulfamoylanthranilic acid (CSA) was found in any plasma or urine samples. CSA was an analytical artifact.

This publication has 12 references indexed in Scilit: