Testing switchability of a new microemulsion formulation of cyclosporine

Abstract

We assessed the bioavailability of cyclosporine (CyA) in the test formulation (Cap Arpimune ME) relative to the reference formulation (Cap Sandimmune Neoral) to ascertain the switchability between the two formulations in patients. The study population included 30 patients on maintenance hemodialysis awaiting renal transplantation. The study adopted a randomized open-label, two-way, two-period, two-sequence crossover design. The dose administered was 8 mg/kg/d in two divided doses for 5 days in each study period with a washout period of 1 week between the two periods. A five-point blood sampling (at 0, 1, 2, 3, and 4 hours postdose) was done on the last day of each study period for CyA level monitoring. The study measures included C max (maximum blood concentration), AUC (area under the blood CyA concentration versus time curve, 0 to 4 hours) and actual time concentrations at individual sampling times. The differences in mean values for all parameters and the least significant differences were less than 20% of reference mean. Assessment of bioequivalence using log-transformed data showed that the point estimate (ratio test: reference) for C max was 0.9717 with a 90% confidence interval (CI) of 0.88 to 1.06 and that for AUC was 1.0053 with a 90% CI of 0.90 to 1.12. The bioequivalence obtained suggests that the test formulation can replace the reference formulation in patients who require CyA therapy.