Pharmacokinetics and biliary excretion of bromosulphophthalein, [3H]-ouabain and [3H]-taurocholic acid in rats with glycerol-induced acute renal failure.

The pharmacokinetics and biliary excretion of bromosulphophthalein (BSP), ouabain and taurocholic acid (TChA) have been studied in rats with glycerol-induced acute renal failure (ARF). In rats with ARF, the hepatic uptake and initial biliary excretion of BSP were decreased. In addition, the rate of BSP conjugation with glutathione by rat liver homogenates was also decreased. This latter change may contribute to the initial decrease in the biliary excretion of BSP. No change was found in the hepatic uptake and biliary excretion of ouabain, but the area under the concentration-time curve was increased and the plasma clearance (Clp) decreased in rats with ARF. This decrease in Clp was not due to reduced renal excretion. The decreased Clp of ouabain in rats with ARF may come from reduced tissue binding and a concomitant decrease in its volume of distribution (Vd). The hepatic handling of TChA appeared unaltered in ARF, but the rate constant for the terminal part of the concentration-time curve (beta) was decreased. This change probably resulted from a large increase in Vd in rats with ARF. It is concluded that the decreased uptake of BSP was not due to a non-specific disturbance of hepatocyte function in ARF because the hepatic handling of ouabain and TChA were unaltered.