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

The study aims at investigating how the drug itraconazole, typically used to fight against fungal infections, is metabolized and distributed within a horse’s body when given either orally or intravenously. The results suggest that oral administration of the itraconazole solution exhibited higher absorption compared to the capsules, and thus, it’s more effective against infections in horses.

Methodology

• The research involved six healthy horses. Itraconazole was administered to the horses in two different formats – as a solution and as capsules.
• The solution was given via a nasogastric tube at a dose rate of 5 mg/kg. After administration, samples of plasma, interstitial fluid (ISF), leukocytes, and aqueous humor were collected from each horse for analysis.
• The second round of the experiment repeated the same process but this time using itraconazole capsules.
• Lastly, three horses were given a 1.5 mg/kg intravenous dosage of itraconazole, with plasma samples obtained subsequently.
• All collected samples were analyzed using high-performance liquid chromatography, and plasma protein binding was determined.

Results

• The study found that itraconazole reached a higher mean concentration in the plasma following the administration of the solution compared to the capsules. This indicates that the body absorbed the drug more effectively when administered as a solution.
• The drug’s bioavailability, which reflects how much of the drug is absorbed and ready to cause an effect, was found to be just over 33% when capsules were administered compared to solution.
• The volume of distribution, which is a measure of how widely the drug spreads in the body, was high and the half-life, depicting how long the drug sustains in the body, was about 11.3 hours. These characteristics align with results seen in other species.
• Itraconazole was not traced in leukocytes, ISF, or aqueous humor, implying the drug does not circulate broadly in the body’s tissues or cells.
• Plasma protein binding was above 98%, suggesting most of the administered itraconazole is bound to plasma proteins and isn’t free to exert a pharmacological effect.

Conclusions

• Overall, it was concluded that the oral administration of the itraconazole solution results in superior drug absorption than the capsules, reaching plasma concentrations that can effectively inhibit horse-specific fungi.
• Given the findings, it is suggested that delivering itraconazole solution orally once every 24 hours could be a useful approach in determining the effectiveness of itraconazole in clinical trials involving horses.