An individual bioequivalence approach to compare the intrasubject variability of two ciclosporin formulations, SangCya and Neoral.
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.
Canafax
D M
DM
SangStat Medical Corporation, Menlo Park, Calif., USA.
Irish
W D
WD
Moran
H B
HB
Squiers
E
E
Levy
R
R
Pouletty
P
P
First
M R
MR
Christians
U
U
D000328:Adult; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency
D004791:Enzyme Inhibitors; D016572:Cyclosporine