Comparison of absorption characteristics of oral reference and compounded itraconazole formulations in healthy cats
Mawby DI, Whittemore JC, Fowler LE, Papich MG
Date: 6 February 2018
OBJECTIVE To compare absorption characteristics of orally administered compounded itraconazole capsules and suspension with those of reference (brand-name) formulations in healthy cats. DESIGN Randomized crossover study. ANIMALS 8 healthy adult cats. PROCEDURES After 12 hours of food withholding, cats received 50 mg of itraconazole (reference capsule, reference solution, compounded capsule, and compounded suspension) in a randomized crossover design, with a 21-day washout period. Capsules were administered with a small meal. Blood samples were collected at predetermined intervals for high-pressure liquid chromatography analysis of plasma itraconazole concentrations. Area under the concentration-time curve, maximum concentration, and terminal half-life of itraconazole were determined and compared among formulations. RESULTS 7 cats completed the study. Mean half-life of itraconazole in reference formulations was 18 to 26 hours. Absorption of the reference solution was 3 times that of the reference capsule. Compounded formulations were absorbed poorly and inconsistently. Complete pharmacokinetic results for the compounded capsule were obtained for only 3 of 6 cats and for the compounded suspension for only 1 of 5 cats, precluding bioequivalence analysis. Relative absorption of compounded formulations was only 2% to 8% of reference formulation values. CONCLUSIONS AND CLINICAL RELEVANCE Compounded oral formulations of itraconazole should not be used for cats because of poor absorption. The differences in absorption between the 2 reference formulations suggested that doses required to meet human target serum concentrations in cats are markedly different (capsules, 12.5 mg/kg [5.7 mg/lb], q 24 h, with food; solution, 4 mg/kg [1.8 mg/lb], q 24 h, without food).
Link to DOI:https://www.doi.org/10.2460/javma.252.2.195