Mawby DL, Whittemore JC, et al. Comparison of absorption characteristics of oral reference and compounded itraconazole formulations in healthy cats. J Am Vet Med Assoc 2018;252:195-200.
Itraconazole, a broad-spectrum synthetic triazole antifungal pharmaceutical, is used in the treatment of both systemic mycoses and dermatophyte infections in cats. This randomized crossover study of eight healthy adult cats compared the absorption characteristics of reference (brand-name) itraconazole capsules and oral suspension with those of orally administered compounded itraconazole capsules and suspension. Itraconazole is highly lipophilic and insoluble in water, and these characteristics contribute to its variable bioavailability and absorption. Compounded formulations of itraconazole are popular, as reference formulations of the drug are expensive, but the former have unknown pharmacokinetics and bioavailability.
The eight cats enrolled in the study had body weights ranging between 3.1 and 5.0 kg (mean, 4.0 kg). The itraconazole formulations, all 50 mg per dose of reference suspension or capsule, and compounded suspension or capsule, were given to the cats after a 12-hour fast in a randomized crossover design with a 21-day washout period between each treatment. Capsuled itraconazole was given with a small meal, as the capsuled formulation of the drug requires administration with some food for optimal bioavailability. No vomiting or regurgitation was observed in any of the animals during any phase of the study. The compounded formulations were prepared by a licensed university pharmacist from a bulk itraconazole powder.
Seven of the eight cats completed the study; one was excluded due to temperament. Absorption of the various formulations of the itraconazole were evaluated based on plasma concentrations of the drug measured over 84-120 hours after administration. Parameters measured included area under the concentration-time curve (AUC), maximum concentration, and terminal half-life of the itraconazole formulations.
The AUC and maximum concentration of the compounded formulations of itraconazole were substantially less than for the reference formulations, and in many instances, plasma concentrations of the drug were undetectable in cats who received compounded formulations. In addition, the reference suspension was much better absorbed (3-4 times) than the reference capsule. The compounded itraconazole capsule formulation demonstrated only 8% of the absorption of the reference capsule, while absorption of the compounded itraconazole suspension was 2% of that of the reference suspension, in the small number of cats in which this could be measured.
Based on the results of this study, the authors recommend use of the commercially available brand-name itraconazole suspension at a dose of 4 mg/kg (1.8 mg/lb) given once daily without food. This is attractive due to the fact that a significantly lower dose of the oral solution is required to achieve therapeutic plasma levels compared to the dose required with brand-name capsules, and because the oral reference suspension can be given without food, unlike the capsules. Now that the US-FDA has recently approved an oral itraconazole suspension for treatment of feline dermatophytosis, the authors also recommend use of this product for treatment of cats with systemic mycoses.
The small number of subjects in this study is a noteworthy limitation. A larger number of study animals, including sick as well as healthy cats, would be required to determine if the absorption characteristics of various formulations of itraconazole as determined in this report are similar in sick cats and larger populations of cats. [PJS]
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