Drug-protein conjugates--IV. The effect of acute renal failure on the disposition of [14C]captopril in the rat.
The effect of acute renal failure (ARF) on the metabolism and covalent binding to plasma proteins (PP) of [14C]captopril [( 14C]CP) was investigated in the Wistar rat in vivo and in vitro using human and rat plasma. In the rat, ARF was induced by parenteral administration of glycerol. Glycerol-induced ARF markedly reduced the renal excretion of [14C]CP, the major route of elimination of the drug in control rats, but did not alter the plasma clearance of [14C]CP. However, there was a significant increase in the plasma concentrations of [14C]CP mixed disulphides with glutathione, cysteine and PP. The increase in mixed disulphide formation did not result in an increase in the concentration of radioactivity in the lung, liver, kidney, spleen or bile. Thus, control rats excreted 9.64 +/- 4.24% of the dose into bile in 3 hr while rats with ARF excreted 7.14 +/- 2.46%. In vitro, [14C]CP reacted rapidly with human or rat plasma to form mixed disulphides with endogenous thiols and PP. With uraemic plasma, there was a significant decrease in the amount of [14C]CP covalently bound to PP from both man and the rat.
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002216:Captopril / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D014508:Urea / Q000097:blood
D001798:Blood Proteins; D002250:Carbon Radioisotopes; D014508:Urea; D011392:Proline; D002216:Captopril; D003404:Creatinine