Plasma protein binding of frusemide in renal failure rabbits: investigation of endogenous protein binding inhibitors.
The reduction mechanism of frusemide-protein binding in the plasma of renal failure was investigated. The drug-albumin binding was inhibited by the low molecular-weight fraction obtained from acute renal failure rabbits, suggesting the presence of the inhibitors in the plasma. Further, this fraction was divided into six subfractions by Bio-Gel P-2. Fractions II and V2 showed significant inhibition of the protein binding of frusemide. Among uraemic toxins, four indole derivatives markedly inhibited the protein binding. Analysis by hplc confirmed that the concentration of indican was markedly increased in acute renal failure rabbit plasma. It is suggested that this compound could be one of the major inducers of the protein binding defect.
D058186:Acute Kidney Injury / Q000097:blood* / Q000139:chemically induced; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002850:Chromatography, Gel / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005665:Furosemide / Q000097:blood*; D007200:Indican / Q000302:isolation & purification / Q000494:pharmacology*; D007210:Indoleacetic Acids / Q000494:pharmacology; D007211:Indoles / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity; D008970:Molecular Weight; D011485:Protein Binding; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000378:metabolism
D001798:Blood Proteins; D007210:Indoleacetic Acids; D007211:Indoles; C014612:indolebutyric acid; D012710:Serum Albumin, Bovine; D008627:Mercuric Chloride; C024139:indole-3-lactic acid; C030737:indoleacetic acid; D005665:Furosemide; D007200:Indican