Conversion from tacrolimus to cyclosporine in stable renal transplant patients - Safety, metabolic changes, and pharmacokinetic comparison

Background. Although conversion between tacrolimus and cyclosporine has bee n performed when indicated for rejection or adverse effects, the safety and metabolic outcome of elective conversion from tacrolimus to cyclosporine h as not previously been examined. Methods. Conversion from tacrolimus to cyclosporine was performed in 19 rec ipients of cadaver renal transplants at 3-6 months after transplantation. P harmacokinetic profiles and biochemical studies were performed three times, in steady state, before, and after conversion. Results. Patient and graft survival was 100% at 3 months after conversion, with no rejection episodes. Three patients have been subsequently converted back to tacrolimus, two for rejection and one for hirsutism. There were no significant changes in creatinine, urate, or blood sugar levels after conv ersion, but the mean plasma magnesium rose from 0.73 (0.63-0.97) to 0.82 (0 .65-1) mmol/L (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4 -6.8) to 5.5 (3.8-7.6) mmol/L (P=0.033). Pharmacokinetic profiles were meas ured before and after conversion, and showed that cyclosporine (Neoral) exh ibited significantly less interpatient and intrapatient variability than ta crolimus, for area under the curve (AUC), maximum concentration after dose (C-max), minimum concentration after dose (C-min), and time to maximum conc entration. Conclusion. This is the first study that has examined the outcome of conver sion from tacrolimus- to cyclosporine-based immunosuppression in stable pat ients after renal transplantation. This conversion was performed without ea rly immunological hazard, but there was a small rise in blood cholesterol l evels after conversion. Pharmacokinetic studies showed that cyclosporine in the form of Neoral exhibited less inter- and intrapatient variability than tacrolimus, although this is of uncertain clinical significance.