Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses.
OBJECTIVE
To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution.


METHODS
6 healthy horses.


METHODS
Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconazole (1.5 mg/kg, IV), and plasma samples were obtained. All samples were analyzed by use of high-performance liquid chromatography. Plasma protein binding was determined. Data were analyzed by compartmental and noncompartmental pharmacokinetic methods.


RESULTS
Itraconazole reached higher mean +/- SD plasma concentrations after administration of the solution (0.41 +/- 0.13 microg/mL) versus the capsules (0.15 +/- 0.12 microg/mL). Bioavailability after administration of capsules relative to solution was 33.83 +/- 33.08%. Similar to other species, itraconazole has a high volume of distribution (6.3 +/- 0.94 L/kg) and a long half-life (11.3 +/- 2.84 hours). Itraconazole was not detected in the ISF, aqueous humor, or leukocytes. Plasma protein binding was 98.81 +/- 0.17%.


CONCLUSIONS
Itraconazole administered orally as a solution had higher, more consistent absorption than orally administered capsules and attained plasma concentrations that are inhibitory against fungi that infect horses. Administration of itraconazole solution (5 mg/kg, PO, q 24 h) is suggested for use in clinical trials to test the efficacy of itraconazole in horses.
Davis
Jennifer L
JL
Clinical Pharmacology Laboratory, Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Salmon
Jacklyn H
JH
Papich
Mark G
MG
D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D017964:Itraconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011485:Protein Binding
D000935:Antifungal Agents; D017964:Itraconazole