Population pharmacokinetics and clinical evaluation of intravenous acetaminophen and its metabolites in Andalusian horses.
Authors: Granados M M, Medina-Bautista F, Navarrete-Calvo R, Argüelles D, Domínguez-Pérez J M, Priego-Capote F, Muñoz-Rascón P, Serrano-Rodríguez J M
Journal: Veterinary journal (London, England : 1997)
Summary
Acetaminophen's intravenous pharmacokinetics and safety profile have remained uncharacterised in horses until now, despite its potential analgesic applications in equine practice. Researchers administered acetaminophen to 20 mares and 20 stallions at two doses (10 and 20 mg/kg), measuring plasma drug concentrations and metabolites (glucuronide and sulphate) via liquid chromatography–mass spectrometry, then constructed population pharmacokinetic models to simulate clinically relevant infusion regimens. Key findings included substantially higher metabolite accumulation than parent drug—glucuronide and sulphate reached 2.1 and 4.53 times the acetaminophen concentration respectively—alongside notable sex-dependent clearance differences, with mares eliminating the drug 34% faster than stallions (0.47 versus 0.35 L/h/kg). Simulated constant-rate infusions yielded therapeutically achievable steady-state concentrations (1.75–5.21 µg/mL for shorter perioperative infusions; 0.62–2.02 µg/mL for prolonged postoperative analgesia), with no adverse clinical, haematological, or biochemical effects observed. These results establish acetaminophen as a safe candidate for equine pain management, though the sex-dependent variability warrants consideration during dose individualisation, and the pronounced metabolite formation may have implications for efficacy and further safety evaluation in clinical settings.
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Practical Takeaways
- •Acetaminophen CRI regimens appear safe in Andalusian horses and warrant clinical trials for perioperative pain management, with potential for both short high-dose infusions (3.33–10 mg/kg/h for 3 h) and longer lower-dose regimens (1.25–3.75 mg/kg/h for 8 h)
- •Sex-dependent pharmacokinetics means mares may require dose adjustment compared to stallions to achieve equivalent steady-state concentrations
- •High metabolite formation suggests monitoring liver function may be prudent in clinical applications, particularly with repeated dosing or in horses with hepatic compromise
Key Findings
- •Acetaminophen clearance differed significantly by sex: mares cleared at 0.47 L/h/kg versus stallions at 0.35 L/h/kg
- •Metabolites accumulated to higher levels than parent drug, with glucuronide 2.1× and sulphate 4.53× higher than acetaminophen at steady state
- •Half-lives were 3.5 h (acetaminophen), 5.6 h (glucuronide), and 3.2 h (sulphate)
- •No adverse effects observed at doses up to 20 mg/kg IV, supporting safety profile for clinical use