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Comparison of absorption characteristics of oral reference and compounded itraconazole formulations in healthy cats

Dianne I. MawbyDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Jacqueline C. WhittemoreDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Leanne E. FowlerDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Mark G. PapichDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Abstract

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).

Abstract

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).

Contributor Notes

Address correspondence to Dr. Mawby (dmawby@utk.edu).