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  • Title: Pharmacokinetics and Relative Bioavailability of Orally Administered Innovator-Formulated Itraconazole Capsules and Solution in Healthy Dogs.
    Author: Hasbach AE, Langlois DK, Rosser EJ, Papich MG.
    Journal: J Vet Intern Med; 2017 Jul; 31(4):1163-1169. PubMed ID: 28627123.
    Abstract:
    BACKGROUND: Itraconazole is commonly used for treatment of systemic and cutaneous mycoses in veterinary medicine. Two formulations, capsule and solution, are used interchangeably in dogs. However, marked differences in bioavailability have been reported in other species. Similar investigations have not been performed in dogs. OBJECTIVE: To determine and compare pharmacokinetics of itraconazole in dogs after oral administration of commercially available capsule and solution formulations intended for use in humans. ANIMALS: Eight healthy, adult, purpose-bred dogs. METHODS: Dogs received approximately 10 mg/kg of innovator-formulated itraconazole solution and capsule PO in randomized, crossover design with a 10-day washout period. To ensure maximal absorption, solution was administered to fasted dogs, whereas capsules were co-administered with food. Blood samples were collected at predetermined time points, and plasma drug concentrations were measured using high-pressure liquid chromatography. Pharmacokinetic parameters were determined with compartmental analysis. RESULTS: The mean relative bioavailability of the capsule was 85% that of the solution, but drug absorption was variable, and overall drug concentrations were similar between formulations. Mean elimination half-lives of both formulations were nearly identical at approximately 33 hours. Regardless of formulation, simulations suggest that a loading dose of 20 mg/kg, followed by 10 mg/kg once every 24 hours, will result in plasma concentrations considered to be adequate in most dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrary to findings reported in other species, overall drug exposures after capsule and solution administration are not substantially different in dogs. Despite some pharmacokinetic differences between itraconazole capsule and solution, formulation-specific dosages do not appear to be necessary.
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