Pharmacokinetics of IV Ketorolac in horses undergoing orchiectomy

Ketorolac (KET) is a nonsteroidal anti-inflammatory drug for human use, with a potent analgesic activity, that is used in the relief of moderate-to-severe postoperative pain. The pharmacokinetics of KET tromethamine was evaluated after single IV injection at 0.5mg/kg body weight, after intubation and 10minutes before surgery, to six Arabian colts undergoing orchiectomy. Intraoperative cardiorespiratory variables were monitored. Blood samples were collected for 36hours, and serum samples were analyzed by high performance liquid chromotography with ultraviolet-visible detection. During surgery, all monitored physiological parameters were stable. Intermittent positive pressure ventilation, and normocapnia were maintained throughout the procedure in all animals. No adverse effects were observed. The kinetics of KET was described by a two-compartment models, and also a noncompartmental analysis was performed. The distribution and elimination half-lives were t1/2λ1 0.06 ± 0.02 and t1/2λ2 0.59 ± 0.21hours, respectively. Body clearance and mean residence time were 339.99 ± 120.19mL/h/kg and 0.49 ± 0.22hours, respectively. The volume of distribution at steady state and volume of distribution based on the terminal phase were 218.83 ± 134.26mL/kg and 522.5 ± 529.3mL/kg, respectively. The serum protein binding was 75.8 ± 2.9%. The results indicate that KET at 0.5mg/kg IV was very rapidly eliminated and thus was likely not effective in the postoperative period. However, further studies including a control group and at higher doses are suggested to investigate the KET kinetics and the analgesic efficacy in horse and define the most appropriate dosage scheme.