No abstract

Serum protein binding of phenylbutazone has been measured in the rat, guinea pig, cat, rabbit and dog, and the influence on it of renal failure induced by uranyl nitrate injection has been studied. In all speciies a clearcut decrease in binding was observed after the occurrence of renal failure; the time course of the fall in binding correlated well with development of renal failure. In further experiments, serum protein binding of two acidic drugs (phenylbutazone, warfarin), two basic drugs (papaverine, quinidine) and one neutral drug (digitoxin) was studied in rabbits with experimental renal failure, and the results compared with those obtained in patients with acute renal failure. In the rabbits, a decrease in the binding of phenylbutazone, warfarin, papaverine and quinidine was found, whereas protein binding of digitoxin was unchanged. In man, there was a definite fall in protein binding of phenylbutazone and digitoxin, a small decrease for warfarin and papaverine, and a slight increase for quinidine.

No abstract

Acute water diuresis and hydropenic studies were carried out in 7 healthy volunteers to investigate the site of action of a new non-sulphonamide diuretic, Bay g 2821. The effects of the drug on the concentrating and diluting mechanism, and on the renal handling of sodium, potassium, calcium, phosphorus and uric acid were studied. The results suggest sites of actions of Bay g 2821 at the proximal tubule and the medullary portion of the ascending limb of the loop of Henle.

Quinidine serum binding is increased in some patients with acute renal failure, but in animals with renal failure conflicting results were published. Therefore, serum binding of quinidine, papaverine and phenylbutazone was studied by equilibrium dialysis in rabbits and rats with acute renal failure induced either by injection of uranyl nitrate or ligation of the ureters. From the results it appears that, in animals, quinidine binding changes are different according to the model used for induction of the renal failure, regardless of the species studied. After ligation of the ureters, lipoprotein concentration increases, but the meaning of this increase for increased serum quinidine binding is not clear.