A PHARMACOKINETIC COMPARISON OF THE CORN-OIL VERSUS MICROEMULSION GELCAP FORMULATION OF CYCLOSPORINE USED DE-NOVO AFTER RENAL-TRANSPLANTATION

The initial poor absorption of the corn oil-based, gel capsule oral fo rmulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during th e early post-transplant period predispose to renal allograft rejection . The present study served to compare the time required to achieve the rapeutic CyA concentrations after de novo administration of the corn o il-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME ; n = 11) formulation of CyA. During the Ist month after renal transpl antation, patients underwent serial pharmacokinetic profiling from whi ch we obtained observed and dose-corrected values of several parameter s. Although patients in neither the CyA-GC nor the CyA-ME group adequa tely absorbed the drug during days 0-2, from day 3 to 4 patients in th e CyA-ME group showed significantly greater absorption than those in t he CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the Ist month target average concentration (C-av) values (greater than or equal to 550 ng/ml) earlier than those in the CyA-GC group and require d significantly lower dally CyA doses (P = 0.018). We conclude that th erapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC.