Pharmacokinetics and efficacy of orallyadministered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia.

Abstract

Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Eight university owned research horses with experimentally induced endotoxemia. Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1mg/kg, PO; FLU), and placebo (PO; PLAC) 2hours 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. Mean maximum plasma APAP concentration was 13.97 ± 2.74 μg/mL within 0.6± 0.3hour after administration. At 4 and 6hours after treatment, both APAP (P= <.001, P= .03, respectively) and FLU (P= .0045 and P< .001, respectively) had a significantly greater decrease in rectal temperature compared to placebo. FLU caused greater heart rate reduction than APAP at 4 and 6hours (P= .004 and P= .04), and PLAC at 4hours (P= .05) after treatment. The pharmacokinetics of acetaminophen in endotoxemic horses differ from thosereportedbyprevious studies in healthy horses. Acetaminophen is an option for antipyresis in clinical cases, particularly when administration of traditional NSAIDs is contraindicated.