title: Administration diluents differentiate Neoral from a generic cyclosporine oral solution.
abstract: A non-microemulsion cyclosporine oral solution was recently recalled from the market because of the lack of bioequivalence when administered with apple juice compared with water as the diluent. This open-label, randomized, two-period, crossover study assessed the effect of apple juice on Neoral, a microemulsion cyclosporine oral solution. The study enrolled 34 subjects who received 180 mg Neoral oral solution diluted in 200 mL tap water or apple juice. Cyclosporine was measured in whole blood by a liquid chromatography method. Pharmacokinetic parameters were compared by standard bioequivalence tests. With water vs. apple juice, cyclosporine Cmax was 1263 +/- 203 vs. 1191 +/- 225 ng/mL and AUC was 4714 +/- 1117 vs. 4788 +/- 1320 ng h/mL, respectively. Bioequivalence was demonstrated for both parameters. These data were comparable with those from a previous study in which subjects received 180 mg Neoral oral solution with orange juice. Cyclosporine bioavailability is unaltered when Neoral is administered diluted in apple juice or orange juice compared with tap water which conforms to the cyclosporine product label.
authors.affiliation: Novartis Pharmaceuticals, Basel, Switzerland. john.kovarik@pharma.novartis.com
authors.forename: John M
authors.initials: JM
authors.lastname: Kovarik
authors.forename: Denise
authors.initials: D
authors.lastname: Barilla
authors.forename: Louis
authors.initials: L
authors.lastname: McMahon
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wang
authors.forename: James
authors.initials: J
authors.lastname: Kisicki
authors.forename: Robert
authors.initials: R
authors.lastname: Schmouder
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D027845:Malus; D012996:Solutions; D013810:Therapeutic Equivalency; D014867:Water
chemical_list: D012996:Solutions; D014867:Water; D016572:Cyclosporine