Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness.

Abstract

Acetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness. To determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness. Longitudinal. Twelve adult horses with chronic lameness were treated with acetaminophen (30 mg/kg PO) every 12 h for 21 days. Plasma concentrations of acetaminophen were analysed on days 7 and 21 via LC-MS/MS and noncompartmental pharmacokinetic analysis. Lameness was evaluated by body-mounted inertial sensor (BMIS) and 10-point subjective lameness score on day 21 and compared to untreated baseline evaluation on day 35. Clinicopathological analysis (n = 12), hepatic biopsy (n = 6) and gastroscopy (n = 6) were evaluated on days -1 and 22. Maximum plasma acetaminophen concentration (Cmax ) was 20.83 ± 10.25 μg/mL at time (Tmax ) 0.40 ± 0.22 h on day 7. The Cmax on day 21 was 17.33 ± 6.91 μg/mL with a Tmax of 0.67 ± 0.26 h. Subjective lameness scores significantly improved at 2 and 4 h post-treatment; Significant percent improvement was detected in PDmax for horses with hindlimb lameness at 1, 2 and 8 h post-treatment. There were no significant differences in gastroscopy or hepatic biopsy scores between days -1 and 22. Small sample size, multi-limb lameness of varying severity and aetiology, lack of intermediary lameness evaluation. In horses with naturally occurring chronic lameness, acetaminophen at 30 mg/kg produced a transient improvement in subjective lameness and BMIS evaluation. Acetaminophen may not be effective as a monotherapy. Acetaminophen was safe following 21 days of 30 mg/kg PO every 12 h, with no evidence of clinically significant changes in clinicopathological analysis, hepatic biopsy or gastric ulceration scores.