CONSISTENT ABSORPTION OF CYCLOSPORINE FROM A MICROEMULSION FORMULATION ASSESSED IN STABLE RENAL-TRANSPLANT RECIPIENTS OVER A ONE-YEAR STUDYPERIOD

To evaluate the pharmacokinetic properties of the new microemulsion fo rmulation of cyclosporine (Sandimmun Neoral), a double-blind, prospect ive study in stable renal transplant recipients was performed, The pat ients were randomized on a 4:1 basis either to receive Sandimmun Neora l (n=45) or continue on regular Sandimmun (n=12). Before randomization , a steady-state pharmacokinetic profile study was performed in all pa tients while they were still on regular Sandimmun. Pharmacokinetic ass essments were then performed after 8 and 12 weeks and after 1 year. A milligram-to-milligram dose conversion was shown to be adequate to mai ntain the patients within a predefined target therapeutic window. Chan ges in pharmacokinetic parameters after conversion to Sandimmun Neoral were consistent with an increased rate and extent of cyclosporine abs orption from the Neoral formulation. This was reflected by a shorter t ime to reach peak concentration and also by a mean increase in peak co ncentration by 67%, and an overall mean increase in drug exposure (are a under the curve) by 34%. These findings were also confirmed 1 year a fter conversion. Furthermore, significantly reduced intraindividual va riability in pharmacokinetic parameters was found, as well as improvem ents in the correlation between trough concentrations and area under t he curve after conversion to Sandimmun Neoral. In conclusion, our resu lts indicate an improved and consistent absorption of cyclosporine fro m the Neoral formulation, which should make clinical management easier and safer.