PHARMACOKINETICS AND THERAPEUTIC MONITORING OF CYCLOSPORINE IN LIVER-TRANSPLANT RECIPIENTS

Cyclosporine (CsA) has played a major role in the development of organ transplantation. However, its use in the prevention of liver graft rejection is somewhat delicate because the liver plays an essential role in the intestinal absorption, metabolism and excretion of CsA. Interindividual differences in CsA pharmacokinetics are large, and clearance can vary by a factor of 40 in liver transplant recipients. During CsA therapy, the intact molecule is assayed in whole blood by means of specific technique. The margin between immunosuppressive and nephrotoxic concentrations is poorly defined. The interpretation of blood concentrations must take into account the mode of administration, associated drug therapy, the time since grafting, and pathological episodes. The recommend trough concentrations are 150-200 ng/ml during the first three months.