Pharmacokinetics of fluconazole following intravenous and oral administration and body fluid concentrations of fluconazole following repeated oral dosing in horses.

The research tested the pharmacokinetics or drug behavior of fluconazole in horses when administered intravenously and orally. The study then measured the concentrations of the drug in body fluids after long-term oral dosing.

Research Methodology

• The experiment involved 6 adult horses that were clinically normal – indicating a lack of major health issues that could affect the study’s results.
• The drug fluconazole, at a dosage of 10 mg/kg of body weight, was given either through an intravenous method or orally to each horse, with a gap of two weeks to allow the drug to be completely metabolized between treatments.
• The researchers monitored plasma concentrations of the drug at various intervals before & after administration: Known time points included at 10 min, 20 min, 30 min, 40 min, 60 min post-administration, and every two hours ranging from 2 hours to 12 hours, followed by after every 12 hours up to 72 hours.
• A long-term dosage plan was formulated where horses received a loading dose of fluconazole (14 mg/kg), followed by a regular dose of 5 mg/kg every 24 hours for 10 days.
• After the final dose administration, fluconazole concentrations were determined in different body fluids including aqueous humor (eye fluid), plasma, cerebrospinal fluid (CSF), synovial fluid (joints), and urine.

Results and Conclusion

• Following oral and intravenous administration, comparable maximum plasma concentrations and terminal half-lives were observed. This suggests that the mode of drug administration did not significantly impact the behavior (absorption, distribution, metabolism & excretion) of the drug.
• The mean volume of distribution of fluconazole at steady state (the point when input of drug is equal to its output) was found to be 1.21±0.01 L/kg, implying fluconazole is fairly distributed across the body fluid compartments.
• The systemic availability and time to reach maximum plasma concentration after oral intake were 101.24±27.50% and 1.97±1.68 hours, respectively, indicating excellent absorption of the drug when given orally and reaching its peak in the body in about 2 hours.
• Long-term oral application retained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses – the concentration necessary to prevent the growth of the fungi.
• Based on the results, the research concludes that fluconazole, given its high bioavailability and effective concentration maintenance, could be a potent therapeutic agent for treating fungal infections in horses.