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PHARMACOKINETICS AND SAFETY OF A SINGLE SUBCUTANEOUS OR INTRAMUSCULAR DOSE OF KETAMINE IN HEALTHY HORSES
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PHARMACOKINETICS AND SAFETY OF A SINGLE SUBCUTANEOUS OR INTRAMUSCULAR DOSE OF KETAMINE IN HEALTHY HORSES

Ana Maria Rangel
Master of Science (MS), Washington State University
07/2025
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Abstract

analgesia NMDA antagonist Subanesthetic use Pharmacology
Background: Pharmacokinetics (PK) of intramuscular (IM) and subcutaneous (SC) administration of ketamine in horses have not been described. Objectives: To describe the PK and safety of ketamine and its metabolites after a single SC or IM administration in horses. Study design: Single-arm, experimental study. Methods: 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 ketamine at 0.5 mg/kg IM. Plasma or serum concentrations of ketamine and its major metabolites were determined by liquid chromatography-mass spectrometry at baseline and selected intervals post-administration. Pharmacokinetic parameters were calculated using both non-compartmental and compartmental analysis. Results: Plasma drug concentrations after SC administration were extremely low (< 5 ng/mL); thus, only IM administration was investigated in phase 2. Median peak serum ketamine concentration after IM administration was 20.9 ng/mL (IQR 15.2 – 35.9) with 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 data (heart rate, respiratory rate, rectal temperature, gastrointestinal sounds, and injection site reactions) or laboratory variables were observed after IM drug administration. Ketamine metabolites were detected within 5 min after IM drug administration. Norketamine was the predominant metabolite. Main limitations: Small sample size, unknown therapeutic plasma concentrations of ketamine and metabolites, large inter-individual variability. Conclusion: Single IM administration of ketamine to healthy horses resulted in rapid drug absorption but highly variable inter-individual ketamine and metabolite concentrations without significant adverse effects. Future studies should evaluate PK of ketamine after repeated IM dosing and determine therapeutic plasma concentrations in horses.

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