Pharmacokinetics of the anti-androgenic drug flutamide in healthy stallions.

This research article analyzes the effects and potential of the anti-androgenic drug flutamide on stallions. The study focuses on the drug’s pharmacokinetics (how the body processes it) and bioavailability in an attempt to find an alternative to surgical castration.

Research Objective

• The primary objective of this research was to examine alternatives to surgical castration for controlling the sexual behavior of intact, or non-castrated, stallions, especially those with breeding potential that participate in training and competition. The research particularly looked into the potency of flutamide, a non-steroidal androgen receptor antagonist known for its anti-androgen effects in humans.

Methodology

• The study involved seven healthy, adult stallions. Four different single doses of flutamide were administered to these horses: 1mg/kg intravenously, 1mg/kg orally in fasted horses, 5mg/kg orally in fasted horses, and 5mg/kg orally in fed horses. These doses were administered randomly at intervals of two weeks.
• Throughout the study, full physical examinations were conducted on the horses and blood samples were collected for pharmacokinetic analyses, complete blood count checks, and biochemistry before and after drug administration. This was done to assess any changes in health due to the administration of flutamide.

Findings

• No abnormalities were found in the physical examinations or blood parameters of the horses after the administration of flutamide, suggesting that the drug might be safe for use in stallions.
• The volume of distribution and clearance of flutamide after intravenous administration was determined to be 0.83L/kg and 1.20L/h/kg respectively. This implies that the drug is quickly distributed throughout the body and removed at a significant rate.
• Flutamide and its main metabolite, 2-hydroflutamide, showed high protein binding values (93-97%), indicating a high affinity for proteins in the blood, which can impact how the drug is distributed and eliminated.
• After oral administration, flutamide was rapidly converted to the active metabolite 2-hydroxyflutamide. The ratio of the concentration of the metabolite to the drug was approximately seven times more, which suggests that much of the administered flutamide gets metabolized.
• The oral bioavailability of flutamide ranged from 6.50% to 6.95%, pointing out that a minor fraction of the orally consumed flutamide is available for the body to use.
• The drug and its metabolite showed a short half-life, meaning they are removed from the body relatively quickly.

Conclusion

• Overall, the research suggests that oral flutamide might reach plasma concentrations effective as an anti-androgenic agent in horses, suggesting a potential alternative to surgical castration. However, further studies are recommended to determine the clinical value of flutamide for controlling sexual behavior in stallions.