title: Bioequivalence of orally administered generic, compounded, and innovator-formulated itraconazole in healthy dogs.
abstract: BACKGROUND
  Itraconazole is commonly used to treat systemic fungal infections in dogs, but problems exist with absorption and cost.
  
  
  OBJECTIVE
  To determine oral bioequivalence of generic and compounded itraconazole compared to original innovator (brand name) itraconazole in healthy dogs.
  
  
  METHODS
  Nine healthy, adult research Beagle dogs.
  
  
  METHODS
  A randomized, 3-way, 3-period, crossover design with an 8-day washout period. After a 12-hour fast, each dog received 100 mg (average: 10.5 mg/kg) of either innovator itraconazole, an approved human generic capsule, or compounded itraconazole (compounded using a commercially available compounding vehicle) with a small meal. Plasma was collected at predetermined intervals for high pressure liquid chromatography analysis. Concentration data were analyzed using noncompartmental pharmacokinetics to determine area under the curve (AUC), peak concentration (C(MAX)), and terminal half-life. Bioequivalence tests compared generic and compounded itraconazole to the reference formulation.
  
  
  RESULTS
  Average ratios of compounded and generic formulations to the reference formulation of itraconazole for AUC were 5.52% and 104.2%, respectively, and for C(MAX) were 4.14% and 86.34%, respectively. A test of bioequivalence using 2 one-sided tests and 90% confidence intervals did not meet bioequivalence criteria for either formulation.
  
  
  CONCLUSIONS
  Neither generic nor compounded itraconazole is bioequivalent to the reference formulation in dogs. However, pharmacokinetic data for generic formulation were similar enough that therapeutic concentrations could be achieved. Compounded itraconazole produced such low plasma concentrations, it is unlikely to be effective; therefore, compounded itraconazole should not be used in dogs.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN.
authors.forename: D I
authors.initials: DI
authors.lastname: Mawby
authors.forename: J C
authors.initials: JC
authors.lastname: Whittemore
authors.forename: S
authors.initials: S
authors.lastname: Genger
authors.forename: M G
authors.initials: MG
authors.lastname: Papich
mesh_terms: D000818:Animals; D019540:Area Under Curve; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D004339:Drug Compounding / Q000662:veterinary*; D016568:Drugs, Generic / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D006207:Half-Life; D017964:Itraconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation; D013810:Therapeutic Equivalency
chemical_list: D016568:Drugs, Generic; D017964:Itraconazole
keywords: Bioavailability; Blastomyces; Fungal infection; Histoplasma; Pneumonia