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

Abstract

BACKGROUND: Acetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness. OBJECTIVES: To determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness. STUDY DESIGN: Longitudinal. METHODS: 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. RESULTS: Maximum plasma acetaminophen concentration (C) was 20.83 ± 10.25 μg/mL at time (T) 0.40 ± 0.22 h on day 7. The Con day 21 was 17.33 ± 6.91 μg/mL with a Tof 0.67 ± 0.26 h. Subjective lameness scores significantly improved at 2 and 4 h post-treatment; Significant percent improvement was detected in PDfor 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. MAIN LIMITATIONS: Small sample size, multi-limb lameness of varying severity and aetiology, lack of intermediary lameness evaluation. CONCLUSIONS: 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.