Accumulation of furancarboxylic acids in uremic serum as inhibitors of drug binding

Clin Chim Acta. 1988 Apr 15;173(2):127-38. doi: 10.1016/0009-8981(88)90250-1.

Abstract

3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, 3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid, 3-carboxy-4-methyl-5-ethyl-2-furanpropionic acid and 3-carboxy-5-propyl-2-furanpropionic acid were detected in uremic serum using gas chromatography-mass spectrometry. Mass chromatography revealed that the serum concentrations of the furancarboxylic acids especially 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, were increased in the chronic hemodialysis patients and that the acids could not be removed by conventional hemodialysis due to their strong binding to plasma protein. 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid was also quantitated in uremic serum by high-performance liquid chromatography. Serum level of the acid in uremic patients showed significant but weak correlation with serum level of urea and duration on hemodialysis. Equilibrium dialysis demonstrated that 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid and 3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid inhibited the bindingof salicylate and 5,5-diphenylhydantoin to albumin. In conclusion, the furancarboxylic acids especially 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were accumulated in uremic serum as inhibitors of drug binding.

MeSH terms

  • Adult
  • Aged
  • Carrier Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Female
  • Furans / blood*
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Propionates / blood*
  • Renal Dialysis
  • Salicylates / metabolism
  • Serum Albumin / metabolism
  • Uremia / blood*

Substances

  • Carrier Proteins
  • Furans
  • Propionates
  • Salicylates
  • Serum Albumin
  • 3-carboxy-4-methyl-5-ethyl-2-furanpropionic acid
  • 3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid
  • 3-carboxy-5-propyl-2-furanpropionic acid
  • 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid