Pharmacokinetics of Intravenous and Oral Tramadol in the Bald Eagle (Haliaeetus leucocephalus)

Abstract

Analgesia is becoming increasingly important in veterinary medicine, and little research has been performed that examined pain control in avian species. Tramadol is a relatively new drug that provides analgesia by opioid (μ), serotonin, and norepinephrine pathways, with minimal adverse effects. To determine the pharmacokinetics of tramadol and its major metabolite O-desmethyltramadol (M1) in eagles, 6 bald eagles (Haliaeetus leucocephalus) were each dosed with tramadol administered intravenously (4 mg/kg) and orally (11 mg/kg) in a crossover study. Blood was collected at various time points between 0 and 600 minutes and then analyzed with high-performance liquid chromatography to determine levels of tramadol and M1, the predominate active metabolite. The terminal half-life of tramadol after intravenous dosing was 2.46 hours. The maximum plasma concentration, time of maximum plasma concentration, and terminal half-life for tramadol after oral dosing were 2156.7 ng/ml, 3.75 hours, and 3.14 hours, respectively. In addition, the oral bioavailability was 97.9%. Although plasma concentrations of tramadol and M1 associated with analgesia in any avian species is unknown, based on the obtained data and known therapeutic levels in humans, a dosage of 5 mg/kg PO q12h is recommended for bald eagles. Pharmacodynamic studies are needed to better determine plasma levels of tramadol and M1 associated with analgesia in birds.