Influence of acute renal failure on the protein binding of drugs in animals and in man.

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.