Interaction between Ciclosporin and Diltiazem in Renal Transplant Patients

J.M. Campistol, Renal Transplant Unit, Hospital Clinic i Provincial, C. Villarroel 170, E-08036 Barcelona (Spain) Dear Sir, Recently, ketoconazole has been proposed to associate with ciclosporin immunosuppressive therapy because of the inhibitory effect on ciclosporin liver metabolism by inhibition P-450 microsomal enzymes, and the financial consequences of this pharmacological interaction [1]. Ciclosporin is extensively metabolized by the liver and excreted via the bile into the feces. Several drugs, besides ketoconazole, have been demonstrated to increase ciclosporin plasma levels by inhibiting the drug metabolism in the liver, such as erythromycin, androg-ens, cimetidine, rifampicine, diphenylhydantoin, and the calcium channel blocker, diltiazem [2]. We present here our preliminary results of this interaction between cyclo-sporin and diltiazem in renal transplant patients. Between January 1988 and January 1989, 82 cadaveric renal transplants were performed in our unit. To determine the protective effect of diltiazem on posttransplant acute tubular necrosis and the inhibition of liver ciclosporin metabolism, we randomized 12 patients with ciclosporin plus diltiazem and 25 with ciclosporin alone. Patients with posttransplant acute tubular necrosis and patients treated with other pharmacological interaction (rifampicine, cimetidine, erythromycin) were excluded from the diltiazem-ciclosporin study. Renal function (serum creatinine), ciclosporin doses (mg/kg/day) and ciclosporin blood levels (RIA-specific monoclonal) were evaluated in both groups at 3, 6, 12 months postkidney transplant. No differences were observed between the two groups in age, weight and sex distribution. Graft survival was 100% at 1 year in both groups, without differences in plasma creatinine at 3, 6 and 12 months posttransplant. Ciclosporin doses were lower during the entire follow-up in the group with diltiazem, Γ300 250 200 150 100 5 6 7 8 9 10