RANDOMIZED, DOUBLE-BLIND, ONE-YEAR STUDY OF THE SAFETY AND TOLERABILITY OF CYCLOSPORINE MICROEMULSION COMPARED WITH CONVENTIONAL CYCLOSPORINE IN RENAL-TRANSPLANT PATIENTS
Ua. Frei et al., RANDOMIZED, DOUBLE-BLIND, ONE-YEAR STUDY OF THE SAFETY AND TOLERABILITY OF CYCLOSPORINE MICROEMULSION COMPARED WITH CONVENTIONAL CYCLOSPORINE IN RENAL-TRANSPLANT PATIENTS, Transplantation, 65(11), 1998, pp. 1455-1460
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.