INFLUENCE OF ACUTE RENAL FAILURE ON PHARMACOKINETICS OF PHENOLSULFONPHTHALEIN IN RATS : A COMPARATIVE STUDY IN VIVO AND IN THE SIMULTANEOUS PERFUSION SYSTEM OF LIVER AND KIDNEY

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The effect of acute renal failure (ARF) on the disposition of phenolsulfonphthalein (PSP) after intravenous administration was investigated in rats. ARF was induced by the subcutaneous injection of uranyl nitrate to rats. Renal excretion of PSP decreased significantly in ARF compared to that in normal controls. On the other hand, rats with ARF showed an increased biliary excretion of PSP to compensate for reduced renal excretion of the drug. Consequently no significant change was found in total body clearance of PSP between control and ARF. The in vitro binding experiment showed that the binding fraction of PSP to ARF plasma was significantly lower than that to control plasma. In order to clarify the regulatory mechanisms of PSP excretion between liver and kidney in ARF, we developed a simultaneous perfusion system of rat liver and kidney, which could control the flow rate and the constituent of the perfusate. In this perfusion system, neither biliary excretion nor the protein binding of PSP differed significantly between control and ARF, though its renal excretion decreased in ARF in a similar manner as in vivo. These results suggest that alterations in plasma protein binding as well as renal excretory function are determinants of PSP disposition in ARF.
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