Pharmacokinetics of the anti-androgenic drug flutamide in healthy stallions.
Authors: Mendoza Francisco Javier, Serrano-Rodriguez Juan Manuel, Buzon-Cuevas Antonio, Perez-Ecija Alejandro
Journal: Veterinary journal (London, England : 1997)
Summary
Surgical castration remains the standard method for managing sexual behaviour in stallions, but alternatives are needed for animals with breeding or performance potential. Mendoza and colleagues investigated whether flutamide, a non-steroidal androgen receptor antagonist already used clinically in humans, could offer a viable pharmacological option by determining its pharmacokinetics and bioavailability across multiple dosing regimens in seven healthy mature stallions. The drug demonstrated a favourable safety profile with no clinical or haematological abnormalities, though oral bioavailability proved disappointingly low at approximately 6.5–7% regardless of fasting status or dose escalation (1–5 mg/kg), with rapid first-pass metabolism to its active metabolite 2-hydroxyflutamide. Despite poor oral absorption, plasma concentrations achieved theoretically sufficient levels to exert anti-androgenic effects, and the metabolite's longer half-life (4.79–6.84 hours versus 1–2 hours for the parent drug) suggests potential for efficacy with appropriately timed dosing intervals. Whilst these pharmacokinetic findings are encouraging, practitioners should recognise that further controlled clinical trials are essential before flutamide can be recommended as a practical castration alternative, particularly given the need to establish effective dosing schedules and confirm sustained behavioural suppression in working stallions.
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Practical Takeaways
- •Flutamide shows promise as a pharmacological alternative to castration for managing stallion behaviour, but current evidence is limited to single-dose safety and kinetic studies without behavioural outcome data
- •The drug is rapidly metabolized to its active form with a short elimination half-life (~2 hours), suggesting frequent dosing intervals may be needed if pursued clinically
- •No safety concerns were identified in this small study, but efficacy and optimal dosing protocols for behaviour modification remain to be established
Key Findings
- •Flutamide oral bioavailability in horses was low at 6.50-6.95% across doses, with rapid conversion to active metabolite 2-hydroxyflutamide (metabolite:drug AUC ratio ~7)
- •Flutamide half-life was approximately 1 hour after IV administration and 2 hours after oral administration, while 2-hydroxyflutamide had longer half-lives of 4.79-6.84 hours
- •Single doses of flutamide up to 5 mg/kg orally produced no abnormalities on physical examination or in blood biochemistry and haematology parameters
- •Oral flutamide achieved plasma concentrations potentially effective as an anti-androgenic agent, but clinical efficacy for controlling sexual behaviour in stallions requires further investigation