Pharmacokinetics and clinical efficacy of acetaminophen (paracetamol) in adult horses with mechanically induced lameness

Background Acetaminophen has been used clinically in horses alone or combined with traditional non-steroidal anti-inflammatory drugs for treatment of musculoskeletal pain in horses. Objectives To determine the pharmacokinetics and efficacy of acetaminophen at two doses in horses with mechanically induced lameness compared with phenylbutazone or placebo control. Study design In vivo experiment. Methods Nine healthy mares with mechanical lameness induced via a reversible sole pressure horseshoe model were treated with acetaminophen (20 mg/kg PO; A20), acetaminophen (30 mg/kg PO; A30), phenylbutazone (2.2 mg/kg, PO; PB) and oral placebo (C) in a randomised four-way Latin square model. Plasma concentrations for A20 and A30 were analysed via LC-MS/MS and noncompartmental pharmacokinetic analysis. Heart rate and heart rate variability were measured using a portable telemetry. Lameness was scored by three blinded boarded equine surgeons using the AAEP and 10-point scales. Results Mean maximum plasma concentration (C-max) for A20 was 20.01 mu g/ml within 0.66 h (T-max) after administration; The mean C-max for A30 was 30.02 mu g/ml with a T-max of 0.43 h. Post-treatment heart rate for A30 was significantly lower than A20 at 1 and 7 h; lower than PB at 2, 3, 4.5 and 7 h; lower than C at 2, 3.5, 4.5, 6, 7 and 8 h. 10-point Lameness scores were significantly improved for A30 than C at 2 and 4 h post-treatment; PB was significantly improved than C at 8 h post treatment. There were no significant differences in lameness between A20, A30 and PB. Main limitations Small sample size, lack of objective lameness measurement. Conclusions Acetaminophen at 30 mg/kg produced a more rapid improvement in lameness scores and heart rate compared with other treatments in this model. Further evaluation of the pharmacokinetics and safety of repeated oral dosing of acetaminophen at 30 mg/kg is needed to determine clinical utility.