Pharmacokinetics and Physiological Effects of a Single Oral Dose of Oxycodone in Healthy Dogs: A Pilot Study.

Abstract

Oxycodone, a full mu opioid receptor agonist prescribed for moderate-to-severe pain in people, could provide outpatient analgesia for dogs with post-operative or cancer pain. To determine the pharmacokinetic profile and physiological side effects of a single oral (PO) dose, five healthy, 2-year-old, castrated male hounds were administered a standard amount of food, with or without immediate-release oxycodone (1 mg/kg), in random order, separated by 1 month. At intervals between 0.25 and 8 h later, blood was sampled to measure plasma oxycodone concentration using ultra high-pressure liquid chromatography with mass spectrometry detection, and vital signs were evaluated. Pharmacokinetic variables were estimated using noncompartmental analysis. Maximum plasma concentration (C_max) was 58.6 (39.3, 61.6) ng/mL, time to maximal plasma concentration (t_max) was 1.5 (0.5, 2.0) h, elimination half-life (t_1/2el) was 2.6 (2.0, 6.7) h, area under the curve from time 0 to last measurement (AUC_0-t) was 236.1 (204.6, 256.0) ng-h/mL, and mean residence time (MRT) was 3.9 (3.4, 9.8) h. Computer simulations using the calculated pharmacokinetic data predicted that 1 mg/kg PO every 6 h would achieve peak (C_max) and trough (minimum plasma concentration, C_min) of 69.4 (60.8, 74.6) and 17.0 (15.5, 46.7), respectively, at steady state. Assuming minimum effective analgesic concentration is similar in humans and dogs (~25 mg/mL), therapeutic concentrations were achieved, but administration more frequently than every 6 h would be necessary. Oxycodone produced a significantly lower rectal temperature 1 and 4 h after administration.