Randomized, International Study of Cyclosporine Microemulsion Absorption Profiling in Renal Transplantation with Basiliximab Immunoprophylaxis

Abstract

Increasing information suggests that absorption profiling may be superior to trough level monitoring for optimal concentration control of cyclosporine microemulsion (Neoral TM ) therapy, and that CsA exposure early post-transplant may correlate significantly with reduced risk of acute graft rejection. This randomized, prospective, multicenter international concentration-controlled study was conducted in 21 renal transplant centers in 8 countries to test and compare the clinical feasibility, functionality, accuracy, precision and prediction of rejection by cyclosporine microemulsion absorption profiling to conventional trough-level drug monitoring. Primary or second renal allograft recipients treated with basiliximab, cyclosporine microemulsion and prednisone immunosup- 157pression were randomized to two study groups in which cyclosporine microemulsion therapy was monitored using a multipointalgorithm or by trough levels. The two study arms were comparable in terms of baseline characteristics, treatment and clinical outcomes. Treatment failure, consisting of acute rejection, graft loss or death, occurred with equal incidence in the two groups (30% and 33%, respectively). Diagnostic feasibility, measured as the proportion of samples obtained within the designated time window, was marginally lower in area under the time-concentration curve (AUC) than in trough groups, but the therapeutic accuracy and precision were comparable or superior in the AUC group. Cox regression analysis performed across study groups showed a highly significant correlation between the predicted probability of acute rejection and cyclosporine (

Evaluation of Cyclosporine and Tacrolimus Dose Changes During Post-transplantation Period and Their Association with Endomyocardial Biopsy Grading

“…However, in some studies, there was no relationship between cyclosporine levels two hours after transplantation (C2) with biopsy grade. As in the study by Cantarovich et al (21), there was no significant differences in C2 between the two groups with EMB grade 2 or less and with grade 3A or higher (22) INT. What seems to explain these differences is that various factors such as the type of immunosuppressive drug (based on our study), along with the administration of ATG or steroid drugs, the initial dosage of the drug, and the follow-up time, can be related to the association between drug dose changes and pathologic grade in endomyocardial biopsy.…”

Change of Cyclosporine Absorption over the Time After Kidney Transplantation

“…Buchler et al have also shown that C0 and C2 blood levels decreased between months 3 and 12 after kidney transplantation (5). In an international study, CsA doses were decreased over the time while the absorptions of drug were increased (11). Most of studies show that CsA dose reduction is safe in long-term transplant patients (2, 12, 13), and this may be because of improvement in drug absorption.…”