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

• Published in: Pharmacology Vol. 59; no. 2; p. 78
• Main Authors: Canafax, D M, Irish, W D, Moran, H B, Squiers, E, Levy, R, Pouletty, P, First, M R, Christians, U
• Format: Journal Article
• Language: English
• Published: Switzerland 01-08-1999
• Subjects: Adult; Cyclosporine - pharmacokinetics; Enzyme Inhibitors - pharmacokinetics; Female; Humans; Male; Middle Aged; Therapeutic Equivalency
• ISSN: 0031-7012
• DOI: 10.1159/000028307

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.