An individual bioequivalence approach to compare the intrasubject variability of two ciclosporin formulations, SangCya and Neoral
Canafax, D. M., Irish, W., Moran, H. B., Squiers, E., Levy, R., Pouletty, P., ... Christians, U. (1999). An individual bioequivalence approach to compare the intrasubject variability of two ciclosporin formulations, SangCya and Neoral. Pharmacology, 59(2), 78-88.
A novel bioequivalence testing approach was used to determine intrasubject variability and switchability of two ciclosporin formulations, SangCya (test) and Neoral (reference). Twenty healthy volunteers were enrolled into a single-dose, randomized, open-label, 4-period, 2-sequence study with a crossover replicate design. Subject-by-formulation interaction variances were compared using a mixed effects linear model. Intrasubject variability for ln AUC(0-infinity) and ln C(max) of SangCya and Neoral were not significantly different. The 95% confidence intervals of the intrasubject variability of AUC(0-infinity) (0.94) and C(max) (1.28) as determined using the bootstrap nonparametric percentile method (n = 2,000) were below the individual bioequivalence limit estimated at 2.25. We concluded equivalent intrasubject variability of ciclosporin pharmacokinetics and switchability between SangCya and Neoral