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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Abstract
The effect of acute renal failure (ARF) on the disposition of phenolsulfonphthalein (PSP) after i.v. administration was investigated in rats. ARF was induced by the s.c. injection of uranyl nitrate to rats. Renal excretion of PSP decreased significantly in ARF compared to that in normal controls. Rats with ARF showed an increased biliary excretion of PSP to compensate for reduced renal excretion of the drug. 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. To clarify the regulatory mechanisms of PSP excretion between liver and kidney in ARF, a simultaneous perfusion system of rat liver and kidney, which could control the flow rate and the constituent of the perfusate, was developed. 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 in vivo. Alterations in plasma protein binding as well as renal excretory function are determinants of PSP disposition in ARF.

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