Pharmacokinetics of oral-transmucosal ketamine in horses

ABSTRACT: Ketamine is a dissociative anesthetic that has been studied as an adjuvant to control acute and chronic pain in humans. This study defined the pharmacokinetics of ketamine after oral-transmucosal (OTM) administration in horses. Six adult crossbred healthy horses (363 ± 34 kg; 8 ± 3 years) received single OTM ketamine doses of 1.5 and 3.0 mg.kg-1. Blood samples were collected over a period of eight hours. Non-compartmental analysis and population pharmacokinetic modeling were carried out. The absolute bioavailability of ketamine after OTM administration in horses was 31.12 ± 10.98% (1.5 mg.kg-1) and 26.44 ± 11.46% (3.0 mg.kg-1). Plasma concentrations were best described by a two-compartment model, assuming the proportional error model, with an absorption duration of a zero-order kinetic process (tk0), and linear elimination. Population estimates were tk0 of 0.19 h, the apparent clearance (CL/F) was 3,462.97 L.h-1, apparent volume of distribution of the central compartment (V1/F) was 1,820.49 L, apparent volume of distribution of the peripheral compartment (V2/F) was 1,317.22 L, and inter-compartmental clearance (Q/F) was 1,084.98 L.h-1. Between-subject variability in CL/F, V1/F, and Q/F best described the data. The covariates body weight and sex were not significant for incorporation in the final model. The population pharmacokinetic model described the plasma concentrations with reasonable precision and predictive power, OTM administration of ketamine in horses is apparently safe, has a high volume of distribution, bioavailability similar to other species, and the maximum concentration in approximately 15 min.