FURTHER INVESTIGATIONS ON THE BINDING OF LOOP DIURETICS TO SERUM PROTEINS FROM PATIENTS WITH LIVER DISEASE

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The binding of three loop diuretics, piretanide, bumetanide and furosemide, to serum proteins from patients with liver cirrhosis of fulminant hepatitis was investigated using equilibrium dialysis. A good correlation was found between serum albumin concentration and the percentage of each unbound (free) loop diuretic in patients with liver disease. The binding data obtained from patients with liver cirrhosis was compared with that of patients with chronic renal failure. Calculations made according to the Sandberg-Rosenthal's formula revealed that the maximum binding concentration (nP) varied in some cases. These findings necessitated a detailed investigation into whether the increased percentage of each unbound loop diuretic in patients with liver disease is attributable not only to lowered serum albumin concentration but also to inhibition of the protein binding by some endogenous substances. Thus, similar experiments were performed using rats with experimental liver cirrhosis. The binding of the loop diuretics to serum proteins in cirrhotic rats differed greatly from the findings obtained from cirrhotic patients. The percentage of unbound loop diuretic was well correlated with serum albumin concentration but not with the concentration of serum bilirubin (an endogenous substance) in cirrhotic rats.