Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals.
Authors: Knych H K, Steffey E P, White A M, McKemie D S
Journal: Equine veterinary journal
Summary
# Tramadol Pharmacokinetics in Neonatal and Young Foals Tramadol is widely used for analgesia in adult horses and other species, yet its pharmacokinetic behaviour in foals younger than six weeks remained uncharacterised, creating uncertainty around appropriate dosing and safety in this critical age group. Researchers administered a single 3 mg/kg intravenous dose of tramadol to eight foals on four separate occasions between days 6–43 of life, collecting serial blood samples over 48 hours to quantify drug and metabolite concentrations and assess behavioural and physiological responses at each developmental stage. Volume of distribution decreased progressively with age (from 5.10 to 3.84 l/kg), whilst clearance remained relatively stable across all age groups (2.69–3.44 l/h/kg), with elimination half-lives consistently between 1.1–1.7 hours regardless of age. Glucuronidation capacity—the foal's ability to metabolise and eliminate the active metabolite O-desmethyltramadol—appeared to mature with age, though the drug was well tolerated throughout, with sedation observed only in the three older cohorts. These findings support tramadol's safety profile in early neonatal foals, though clinicians should recognise that therapeutic analgesic concentrations in this population remain to be established, and further work is needed before confident clinical recommendations can be made for pain management in foals under six weeks old.
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Practical Takeaways
- •Tramadol at 3 mg/kg IV is safe for pain management in foals from 1-6 weeks of age, with dosing consistency across this age range appearing appropriate
- •Young foals (6-8 days) show higher drug distribution and clearance; monitor for differences in drug response compared to older foals despite similar half-lives
- •Sedation becomes a notable effect in foals older than 2 weeks, which may be useful therapeutically but requires awareness when using tramadol for analgesia
Key Findings
- •Volume of distribution decreased with age from 5.10 l/kg at 6-8 days to 3.84 l/kg at 40-43 days
- •Clearance decreased with age from 3.44 l/h/kg at 6-8 days to 2.69 l/h/kg at 40-43 days
- •Elimination half-life remained consistent across age groups (1.13-1.73 hours), showing no significant age-related differences
- •Glucuronidation capability increased with foal age; tramadol was well tolerated at all ages with sedation observed in foals aged 13+ days