Effect of cyclosporin A on bile flow in experimental animals using technetium-99m EHIDA

The effect of cyclosporin A (CyA) on bile flow was studied in experimental rabbits by radionuclide imaging and measurement of bilirubin levels. The rabbits were dosed intravenously with 15 mg/kg CyA for 4 consecutive days. Each rabbit served as its own control. The rabbits were injected IV with technetium (Tc)-99m EHIDA, and dynamic images were obtained prior to and 1, 4, 8, and 15 days after CyA treatment. There was no difference in half-times of blood clearance in control and CyA-treated rabbits. There were differences in the half-times of liver curve and bilirubin measurements between control and 4-day treated rabbits. By the 15th day after CyA treatment both the radionuclide findings and bilirubin levels became normal. The results suggest that CyA causes intrahepatic cholestasis and demonstrate evidence of reversibility of CyA's toxic effect on bile flow after treatment is discontinued.