Bioequivalence of Orally Administered Generic, Compounded, and Innovator-Formulated Itraconazole in Healthy Dogs

BackgroundItraconazole is commonly used to treat systemic fungal infections in dogs, but problems exist with absorption and cost. ObjectiveTo determine oral bioequivalence of generic and compounded itraconazole compared to original innovator (brand name) itraconazole in healthy dogs. AnimalsNine healthy, adult research Beagle dogs. MethodsA randomized, 3-way, 3-period, crossover design with an 8-day washout period. After a 12-hour fast, each dog received 100mg (average: 10.5mg/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. ResultsAverage 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. Conclusion and Clinical ImportanceNeither 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.