The effect of acute renal failure on the pharmacokinetics of indocyanine green in the rat

The pharmacokinetics of indocyanine green (ICG) have been studied in control rats and rats with acute renal failure (ARF). Three models of ARF were investigated, and these were produced in the following ways: by bilateral ureteral ligation (surgical model), or by parenteral injection of either uranyl nitrate or glycerol. In both control and uraemic rats, from all three models of ARF, the plasma disappearance of ICG was biexponential and from the plasma disappearance curves the rate constants for transfer from plasma to liver (k₁₂), liver to plasma (k₂₁); and liver to bile (k₂₃) were calculated. The initial removal of ICG from plasma was significantly slowed and k₁₂ significantly decreased in male rats with surgically or uranyl nitrate-induced ARF. The plasma clearance of ICG was not affected by surgically-induced ARF but clearance was reduced in the uranyl nitrate model. More complex changes occurred in male rats with glycerol-induced ARF as k₁₂, k₂₁, k₂₃ and plasma clearance of ICG were all significantly decreased. Female rats with glycerol-induced ARF showed significant decreases in k₁₂, and plasma clearance, but these changes were much smaller than in uraemic males.Of the three models of ARF studied the glycerol model was preferred because surgery alone had a pronounced effect upon the kinetics of ICG and wet liver weight was significantly decreased in the uranyl nitrate model. These changes complicated interpretation of the results from the surgical and uranyl nitrate models. The results from the glycerol model suggest that the hepatic uptake of ICG, and possibly its biliary excretion, were reduced in rats with ARF. In addition, liver function in female rats appears to be more resistant than that in males to the effects of glycerol-induced ARF.