Pharmacokinetics of Intramuscularly Administered Ketamine at Subanaesthetic Dosage in Horses

Subanaesthetic doses of ketamine (0.5 mg kg^-1) provide analgesia in several species, but there is limited information on the pharmacokinetics and clinical effects of intramuscularly administered ketamine in horses. This study investigated the pharmacokinetics of ketamine and norketamine, and evaluated clinical effects, ataxia, and vital parameters, following intramuscular and intravenous administration of 0.5 mg kg^-1 ketamine in nine healthy horses, using a randomized two-period crossover design with a 1-week washout period. Plasma concentrations were analyzed using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS). Ketamine pharmacokinetic parameters were calculated using a one-compartment model and norketamine using a noncompartmental model. After intravenous administration (n = 9), ketamine showed a C_max of 525 ± 290 ng mL^-1, an AUC_0-∞ of 85.9 ± 54.7 ng·h mL^-1, and a t_1/2z of 0.1 ± 0.01 h. Following intramuscular administration (n = 7), ketamine plasma concentrations were below the limit of quantification (< 5 ng mL^-1) except at a few early timepoints, preventing reliable pharmacokinetic analysis. Norketamine showed a C_max of 39.7 ± 32.3 ng mL^-1 and a t_max of 0.3 ± 0.18 h after intramuscular administration. All horses developed transient, mild-to-severe ataxia after intravenous administration, resolving within 15 min. This was not observed after intramuscular administration. Intramuscular ketamine administration (0.5 mg kg^-1) shows a low systemic bioavailability (< 5%) but is well tolerated and has minimal adverse effects.