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Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses

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  • 1 Clinical Pharmacology Laboratory, Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 2 Comparative Ophthalmology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 3 Clinical Pharmacology Laboratory, Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Abstract

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.

Animals—6 healthy horses.

Procedure—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 µg/mL) versus the capsules (0.15 ± 0.12 µg/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 and Clinical Relevance—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. (Am J Vet Res 2005;66:1694–1701)

Abstract

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.

Animals—6 healthy horses.

Procedure—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 µg/mL) versus the capsules (0.15 ± 0.12 µg/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 and Clinical Relevance—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. (Am J Vet Res 2005;66:1694–1701)