RANDOMIZED, DOUBLE-BLIND, ONE-YEAR STUDY OF THE SAFETY AND TOLERABILITY OF CYCLOSPORINE MICROEMULSION COMPARED WITH CONVENTIONAL CYCLOSPORINE IN RENAL-TRANSPLANT PATIENTS

Background. A microemulsion formulation of cyclosporine, Neoral, has b een developed to overcome the problems associated with the poor and va riable absorption of the traditional oil-based oral formulation, Sandi mmune. The present study was conducted to compare the safety and toler ability of Neoral versus Sandimmune in maintenance renal transplant re cipients over 1 year, and to assess the number of dose adjustments nec essary to maintain trough cyclosporine concentrations within the desir ed therapeutic range. Methods. Patients on Sandimmune were randomized to be converted to Neoral (n=373) or remain on Sandimmune (n=93) for 1 2 months. Results. The proportion of patients needing dose increases t o maintain cyclosporine trough levels within the desired range was sig nificantly higher in the Sandimmune group during the first 3 months of the study, whereas the number of patients needing dose reductions was similar in both groups throughout the study period. There were no dif ferences between the groups in terms of changes in blood pressure, ser um creatinine levels, or other laboratory parameters. No significant d ifferences in the incidence of adverse events known to be related to c yclosporine were observed between the treatment groups. More adverse e vents were causally related to Neoral than to Sandimmune by the invest igators. However, overall, there were no clinically relevant differenc es between the treatment groups in the main safety and tolerability va riables. Conclusions. The results of this study in maintenance renal t ransplant patients suggest that the improved pharmacokinetic character istics of the microemulsion formulation of cyclosporine, Neoral, may f acilitate the clinical management of cyclosporine immunosuppression, c ompared with the traditional formulation, Sandimmune. Furthermore, the re is no evidence that the average improved bioavailability of Neoral has a negative impact on the main safety and tolerability variables, a s no significant differences in graft function, the incidence of rejec tions, and most adverse events were seen.