Pharmacokinetics and Safety of a Single Subcutaneous or Intramuscular Dose of Ketamine in Healthy Horses

Pharmacokinetics (PK) of intramuscular (IM) and subcutaneous (SC) ketamine in horses has not been described. This study aimed to evaluate the PK and safety of ketamine and its metabolites after a single SC or IM administration. In Phase 1, two horses received 0.5 or 1 mg/kg of ketamine via SC and IM routes. In Phase 2, eight horses received 0.5 mg/kg IM. Plasma or serum concentrations of ketamine and major metabolites were determined by a validated liquid chromatography-mass spectrometry method at baseline and selected intervals post-administration. Subcutaneous administration resulted in extremely low concentrations (< 5 ng/mL). Phase 2 focused only on IM administration. Median peak serum ketamine concentrations after IM administration were 20.9 ng/mL (IQR 15.2-35.9) with a time to peak drug concentration of 1.4 h (IQR = 0.8-1.9 h) and terminal half-life of 1.8 h (IQR = 1.3-2.6 h). No changes in physical examination or laboratory parameters were observed. Ketamine metabolites were detected within 5 min after IM administration, with norketamine as the predominant metabolite. A single IM administration in healthy horses resulted in rapid absorption and variable inter-individual concentrations without adverse effects. Future studies should investigate repeated IM dosing and determine therapeutic plasma concentrations in horses.