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