Itraconazole disposition after single oral and intravenous and multiple oral dosing in healthy cats

Objective - To determine the disposition of itraconazole in cats after single IV and oral dosing (as a solution or capsule) and multiple oral (capsule) dosing, and to establish bioavailability after oral administration of the solution. Animals - 6 healthy cats for experiment 1 (E1), and 12 cats for experiment 2 (E2). Procedure - For E1 (nonrandomized crossover design), each cat received a single dose of itraconazole solution (5 mg/kg of body weight) orally, and 1 month later, another dose IV. Blood samples were collected for 96 hours. For E2, each cat was given either 5 (group [G] 1) or 10 (G2) mg of itraconazole/kg (capsules) twice daily for 6 weeks. Samples were collected for 96 hours after the first and last dose. Itraconazole was detected by use of high-performance liquid chromatography. Results - For E1, itraconazole plasma drug concentration extrapolated to time zero (IV dose) was 5.2 ± 1.4 μg/ml, and mean residence time (MRT) was 37 ± 16 hours. For oral dosing, maximal itraconazole concentration was 1.69 ± 0.864 μg/ml, MRT was 48 ± 17 hours, and bioavailability was 78.8 ± 28%. For the multiple oral dosing study, MRT (at last dose: 81.1 ± 97.4 hours for G1, and 63.1 ± 15.1 hours for G2) was shorter (P = 0.02) at first dose, compared with last dose, for both groups but did not differ between groups. Maximal concentration did not differ between groups at either time. Steady state was achieved at 14 to 21 days. All cats tolerated itraconazole with no evidence of adverse effects. Conclusions - The oral itraconazole solution is preferred to capsules; a 24-hour dosing interval should be sufficient; 10 mg/kg given daily should generate therapeutic concentrations in most cats; steady-state concentrations may take up to 3 weeks to achieve; and cats appear to tolerate itraconazole well.