DECREASED BINDING OF DRUGS AND DYES TO PLASMA PROTEINS FROM RATS WITH ACUTE RENAL FAILURE: EFFECTS OF URETER LIGATION AND INTRAMUSCULAR INJECTION OF GLYCEROL

1 The decreased binding of drugs and dyes to plasma proteins from male and female rats with acute renal failure has been investigated using equilibrium dialysis at 37°C. 2 Acute renal failure induced by bilateral ligation of the ureters produced a greater than threefold increase in the unbound fraction of o‐methyl red relative to normal rat plasma. Unbound dye concentration in plasma from sham‐operated control rats was also significantly increased but to a lesser extent. 3 Glycerol‐induced acute renal failure produced a significant increase in the unbound fractions of o‐methyl red, methyl orange, bromocresol green (BCG), 2‐(4′‐hydroxybenzeneazo) benzoic acid (HABA), phenytoin and salicylic acid. A marginally significant increase in unbound warfarin concentration was observed. 4 Glycerol‐induced renal failure had no effect on total plasma protein concentration and experiments with o‐methyl red and salicylic acid indicated that a direct effect of glycerol was not responsible for the diminution of binding. 5 Glycerol‐induced acute renal failure, which produced decreases in drug and dye binding similar to those reported for human uraemic plasma, provides a convenient non‐surgical animal model for the investigation of this phenomenon.