Characterization of the Pharmacokinetics and Physiological Effects of Tapentadol in Horses

Tapentadol is a dual mechanism analgesic utilizing both μ‐opioid receptor (MOR) agonism and norepinephrine reuptake inhibition (NRI). This study evaluated the pharmacokinetics and pharmacodynamics of tapentadol as a potential analgesic with the goal of treating pain in horses. Pharmacokinetics of both tapentadol and tapentadol‐O‐glucuronide were elucidated. Six horses received three separate escalating single oral doses (1, 3, and 5 mg/kg) and a single intravenous (0.32 mg/kg) dose of tapentadol in a four‐period sequential design. Concentrations of tapentadol and tapentadol‐O‐glucuronide were determined using liquid chromatography–tandem mass spectrometry. The maximum concentrations (mean ± SD) in plasma following administration of 1, 3, 5 mg/kg oral tapentadol were 7.98 ± 6.95, 39.8 ± 53.8, and 210.6 ± 234.4 ng/mL at 0.75, 0.63, and 0.38 h, respectively. Maximum plasma concentration (mean ± SD) after a single 0.32 mg/kg IV dose was 339.2 ± 83.5 ng/mL. The maximum concentrations of tapentadol‐O‐glucuronide following single 1, 3, and 5 mg/kg oral doses and a single 0.32 mg/kg IV dose of tapentadol were 532.6 ± 171.4, 1169.4 ± 345.4, 1559.5 ± 574.6, and 226.4 ± 51.5 ng/mL at times 6.0, 6.0, 7.0, and 0.5 h. Tapentadol was well‐tolerated at all doses.