Resistance of proteinuric rats to furosemide: Urinary drug protein binding as a determinant of drug effect

Thomas P. Green*, Bernard L. Mirkin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The effect of drug binding to urinary proteins on the diuretic response to furosemide was assessed in normal and nephrotic rats. Nephrosis was induced by treating Sprague-Dawley rats with puromycin aminonucleoside. Binding of furosemide to urinary proteins was found to range from 60 to 95% depending on the concentration of urinary protein. The diuretic response to furosemide reaching the renal tubular lumen was inversely correlated with the degree of proteinuria, a finding that was independent of serum protein concentration of glomerular filtration rate. These data suggest that the binding of furosemide to urinary protein decreases the diuretic effect of furosemide and that drug-protein interactions of this type may also be important in modulating the activity of other lumenally-active drugs or endogenous substances exhibiting a high degree of protein binding. The binding of furosemide to urinary protein may explain the refractoriness of some patients with proteinuria to this agent.

Original languageEnglish (US)
Pages (from-to)623-630
Number of pages8
JournalLife Sciences
Volume26
Issue number8
DOIs
StatePublished - Feb 25 1980

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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