Effect of Rifampicin on Cyclosporin A Blood Levels in a Renal Transplant Recipient

Dr. M.J.D. Cassidy, Departments of Medicine and Surgery, University of Cape Town, Medical School and Groote Schuur Hospital, Cape Town (South Africa) Dear Sir, Rifampicin is a powerful enzyme inducer acting on the cytochrome P 450 enzyme system in the liver and thus may affect the metabolism of a number of drugs [1]. The interaction of rifampicin with glucocorticoids is well recognised and the adverse effect of this combination of drugs on renal allograft function has previously been reported [2]. It has been recommended that renal transplant recipients have their dose of prednisolone increased, by a factor of at least 2, should they be treated concurrently with rifampicin [3]. We report on a renal transplant recipient who developed low whole blood levels of cyclosporin whilst being treated with rifampicin for tuberculosis. A 57-year-old man with Balkan ne-hropathy and end-stage renal failure received a cadaveric renal allograft in March 1984. He had a past history of pulmonary tuberculosis and a grossly abnormal chest radiograph. At the time of surgery he received 250 mg of methylprednisolone intravenously, and immunosup-pression was achieved thereafter with methylprednisolone, 24 mg/day by mouth and cyclosporin A, 4 ml twice daily (13 mg/kg/day) diluted in orange juice. In addition, antituberculous therapy consisting of isoniazid, 300 mg, pyrazinamide 1,500 mg, and rifampicin, 450 mg, daily was commenced. There was immediate graft function following transplantation, the serum creatinine falling to 334 μmol/l (3.8 mg/dl) by day 2 and 165 μmol/l (1.9 mg/dl) by day 20 after transplantation. Whole blood cyclosporin levels (Sandoz Radioimmunoassay) fell progressively and remained low despite an increased dose of cyclosporin. Blood samples were drawn for the trough levels 1 h prior to the administration of the morning dose of cyclosporin and the peak levels were obtained at 4 h following the dose. On the withdrawal of rifampicin, blood levels of cyclosporin rose dramatically (fig. 1). Renal function has remained satisfactory and cycloCyclosporin dose, ml 9 9 8 8 8 8 8 9 10 10 10 10 10 10 10 10 9.5 95 9 9