An individual bioequivalence approach to compare the intrasubject variability of two ciclosporin formulations, SangCya (TM), and Neoral (R)

Citation
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
Citations number
36
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOLOGY
ISSN journal
00317012 → ACNP
Volume
59
Issue
2
Year of publication
1999
Pages
78 - 88
Database
ISI
SICI code
0031-7012(199908)59:2<78:AIBATC>2.0.ZU;2-5
Abstract
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.