Binding of drugs in serum, blood cells and tissues of rabbits with experimental acute renal failure.

In vitro binding of phenylbutazone and phenytoin was studied in serum in tissue homogenates, in tissue slices and in blood cells of rabbits with acute renal failure induced by uranyl nitrate. For phenylbutazone serum binding was decreased in uraemic rabbits, while the binding in homogenates of kidneys and liver was increased. For phenytoin binding in serum and in homogenates and slices of kidneys was decreased in uraemic rabbits. Binding of phenylbutazone and phenytoin to blood cells was not significantly changed in uraemic rabbits. The changes in tissue binding found are small and are only significant for liver and kidney which represent a small fraction of total body mass. Although the methodology for measurement of tissue binding is not entirely satisfactory, we think we can conclude that these changes probably contribute only to a minor degree to the increase of the volume of distribution found for these drugs in renal failure as already suggested by our in vivo data in the preceding paper.