Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia

Abstract Background Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. Objectives To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Animals Eight university owned research horses with experimentally induced endotoxemia. Methods Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1 mg/kg, PO; FLU), and placebo (PO; PLAC) 2 hours after administration of LPS. Plasma APAP was analyzed via LC‐MS/MS. Serial CBC, lactate, serum amyloid A, heart rate and rectal temperature were evaluated. Serum IL‐1β, IL‐6, IL‐8, IL‐10, and TNF‐α were evaluated by an equine‐specific multiplex assay. Results Mean maximum plasma APAP concentration was 13.97 ± 2.74 μg/mL within 0.6 ± 0.3 hour after administration. At 4 and 6 hours after treatment, both APAP (P =