Biliary Excretion of Cyclosporine in Liver Transplant Patients.

Abstract

Cyclosporine (CyA) is a novel cyclic polypeptide with potent immunosuppressive properties.1,2 CyA is presently used with steroids to prevent the rejection of transplanted kidneys,3 livers,4 and hearts.5,6 This drug is primarily eliminated from the body by hepatic metabolism, and biliary excretion is the major route of CyA elimination in animals.7 In humans, enterohepatic recycling of CyA has been suggested because of the presence of a second peak in CyT (CyA plus metabolites measured by radioimmunoassay [RIA)) plasma concentrations and the appearance of the drug in the ileostomy drainage of one patient.8 We have observed increases in CyA blood levels (parent compound measured by high-pressure liquid chromatography [HPLC]) following T-tube clamping in liver transplant patients, which is also indicative of possible enterohepatic recycling of CyA. In order for CyA to undergo any significant enterohepatic recirculation, large amounts of CyA must be excreted in the bile. In the present study, we quantitated the biliary excretion of CyA and CyT in adult liver transplant patients in order to determine whether CyA undergoes significant enterohepatic recycling.