[Cyclosporin interactions in kidney transplants]

Abstract

Treatment with Cyclosporine has resulted in improved allograft survival. Cyclosporine metabolism occurs in the liver via hepatic cytochrome P-450IIIA microsomal enzyme. Pharmacokinetic drug interactions usually involve drugs which induce or inhibit the cytochrome P-450 system. We reviewed the Medical Charts of 53 renal transplant recipients immunosuppressed with Cyclosporine between 1985 and 1991. We analysed the relationship between Cyclosporine concentration, its dose and the change induced by concomitant administration of different drugs. Until December 1988, Cyclosporine was measured by solid-phase radioimmunoassay (RIA) using a polyclonal antibody. This method measures Cyclosporine and some of its metabolites. Since January 1989, Cyclosporine was measured in whole blood by radioimmunoassay (RIA-Kit Sandimmun, Sandoz), which used a specific monoclonal antibody which binds Cyclosporine and a non-specific monoclonal antibody which binds Cyclosporine and its metabolites. The therapeutic range recommended by Sandoz in whole blood using the specific monoclonal antibody is 100 to 400 ng/ml. We present 3 cases of probable pharmacokinetic drug interactions with Cyclosporine. The first patient received concomitantly isoniazide (150 mg/day). Cyclosporine levels were between 600 and 2085 ng/ml despite the dose reduction from 10 to 1.5 mg/kg/day (Fig. 1). The dose reduction of isoniazide to 100 mg/day resulted in reduction of Cyclosporine levels. Until December 1988 with the polyclonal antibody the median was 320 ng/ml (range: 185 to 760 ng/ml; n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)