Bioequivalence of Orally Administered Generic, Compounded, and Innovator-Formulated Itraconazole in Healthy Dogs
Article first published online: 1 NOV 2013
Copyright © 2013 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 28, Issue 1, pages 72–77, January/February 2014
How to Cite
Mawby, D.I., Whittemore, J.C., Genger, S. and Papich, M.G. (2014), Bioequivalence of Orally Administered Generic, Compounded, and Innovator-Formulated Itraconazole in Healthy Dogs. Journal of Veterinary Internal Medicine, 28: 72–77. doi: 10.1111/jvim.12219
- Issue published online: 15 JAN 2014
- Article first published online: 1 NOV 2013
- Manuscript Accepted: 10 SEP 2013
- Manuscript Revised: 31 JUL 2013
- Manuscript Received: 15 MAY 2013
- Companion Animal Fund
- Fungal infection;
Itraconazole is commonly used to treat systemic fungal infections in dogs, but problems exist with absorption and cost.
To determine oral bioequivalence of generic and compounded itraconazole compared to original innovator (brand name) itraconazole in healthy dogs.
Nine healthy, adult research Beagle dogs.
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 (CMAX), and terminal half-life. Bioequivalence tests compared generic and compounded itraconazole to the reference formulation.
Average ratios of compounded and generic formulations to the reference formulation of itraconazole for AUC were 5.52% and 104.2%, respectively, and for CMAX 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 Importance
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.