Pharmacokinetics of cyclosporine and nephrotoxicity in orthotopic liver transplant patients rescued with FK 506.

Abstract

Cyclosporine (CyA) has been used extensively in organ transplantation, but its use is limited by its nephrotoxicity.1 FK 506 is a novel immunosuppressive drug that synergizes with CyA in in vitro and in animal studies.2,3 Combination therapy of FK 506 and CyA appears to be effective in clinical trials. However, preliminary animal studies have shown FK 506 to also be nephrotoxic.4 In initial clinical trials, combined use of CyA and FK 506 resulted in severe renal dysfunction.5 The mechanistic basis for this observation is not completely understood. The aim of the present study is: (1) to evaluate the kinetics of CyA before and during FK 506 therapy in orthotopic liver transplant (OLTx) patients, in order to determine the presence of any pharmacokinetic drug interaction; (2) to determine the changes in serum creatinine during the study period; and (3) to monitor terminal disposition half-life of CyA after the drug is discontinued in patients receiving FK 506 therapy.