Dm. Canafax et al., An individual bioequivalence approach to compare the intrasubject variability of two ciclosporin formulations, SangCya (TM), and Neoral (R), PHARMACOL, 59(2), 1999, pp. 78-88
A novel bioequivalence testing approach was used to determine intrasubject
variability and switchability of two ciclosporin formulations, SangCya(TM)
(test) and Neoral(R) (reference). Twenty healthy volunteers were enrolled i
nto 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 In AUC(0-infinity), and In C-max of SangCya and Neoral were not signifi
cantly different. The 95% confidence intervals of the intrasubject variabil
ity of AUC(0-infinity) (0.94) and C-max (1.28) as determined using the boot
strap nonparametric percentile method (n = 2,000) were below the individual
bioequivalence limit estimated at 2.25. We concluded equivalent intrasubje
ct variability of ciclosporin pharmacokinetics a nd switchability between S
angCya and Neoral.