Bioequivalence of Neoplanta capsule to Sandimmune Neoral, microemulsion formulations of cyclosporin A in human subjects.

摘要

A bioequivalence study of the Neoplanta capsule to the Sandimmune Neoral capsule, microemulsion formulations of cyclosporin A (CyA), was conducted. Twenty-four healthy Korean male subjects received each formulation at the CyA dose of 175 mg in a 2 x 2 crossover study. There was a 2-week washout period between the doses. Blood concentrations of CyA were monitored by a radioimmunoassay for over a period of 48 h after the administration. AUCinf (area under the blood concentration/time curve from time zero to infinity) was calculated by the linear-log trapezoidal method. Cmax (maximum blood drug concentration) and Tmax (time to reach Cmax) were compiled from the blood concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCinf and Cmax and untransformed Tmax. There were no significant differences between the formulations in these parameters. The point estimates and 90% confidence intervals for AUCinf (parametric), Cmax (parametric) and Tmax (nonparametric) were, in point estimate (90% confidence interval), 0.978 (0.937 approximately 1.02), 0.954 (0.900 approximately 1.01) and 0.000 (-0.125 approximately 0.000), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the U.S. Food and Drug Administration guidelines. Moreover, the modified Pitman-Morgan's adjusted F test and equal variance test (1-sided) indicated that the 2 formulations were comparable in intra- and interindividual variability in CyA bioavailability. Therefore, these results indicate that the 2 formulations of CyA are bioequivalent and, thus, may be prescribed interchangeably.