Pharmacokinetics of ketamine and its metabolite norketamine administered at a sub-anesthetic dose together with xylazine to calves prior to castration

The objective of this study was to evaluate the plasma pharmacokinetics of ketamine and its active metabolite norketamine administered intravenously at a dose of 0.1 mg/kg together with xylazine (0.05 mg/kg) to control the pain associated with castration in calves. A two-compartment model with an additional metabolite compartment linked to the central compartment was used to simultaneously describe the time-concentration profiles of both ketamine and its major metabolite norketamine. Parameter values estimated from the time-concentration profiles observed in this study were volume of the central compartment (V_c = 132.82 ± 68.23 mL/kg), distribution clearance (CL_D = 15.49 ± 2.56 mL/min/kg), volume of the peripheral compartment (V_T = 257.05 ± 41.65 mL/kg), ketamine clearance by the formation of the norketamine metabolite (CL_2M = 8.56 ± 7.37 mL/kg/min) and ketamine clearance by other routes (CL_o = 16.41 ± 3.42 mL/kg/min). Previously published data from rats suggest that the metabolite norketamine contributes to the analgesic effect of ketamine, with a potency that is one-third of the parent drug. An understanding of the time-concentration relationships and the disposition of the parent drug and its metabolite is therefore important for a better understanding of the analgesic potential of ketamine in cattle.