Morphine in donkeys: Antinociceptive effect and preliminary pharmacokinetics.

Abstract

BACKGROUND: Morphine is the prototypical &#x3bc;-opioid receptor agonist used to provide analgesia in veterinary species. Its effects are well-described in horses but not donkeys. OBJECTIVES: To determine the antinociceptive effects of two doses of morphine in donkeys. To describe preliminary pharmacokinetic parameters of morphine in donkeys. STUDY DESIGN: In vivo experiment. METHODS: Eight adult castrated male donkeys were given intravenous (IV) 0.9% saline, morphine 0.1&#xa0;mg/kg bwt (LDM), or morphine 0.5&#xa0;mg/kg bwt (HDM) in a randomised order with a minimum 1-week washout period. Mechanical nociceptive thresholds (MNTs) were determined by a blinded investigator pre-injection and 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, and 360&#x2009;min post-injection. Venous blood samples were collected pre-injection and 2, 5, 10, 15, 30, 45, 60, 90, and 120&#x2009;min post-injection. Data were analysed using Friedman's test with Dunn's post hoc test for multiple comparisons. Pharmacokinetic parameters were calculated for the HDM treatment. RESULTS: Baseline MNT was [median (interquartile range)] 8.9 (7.1-10.3) N and did not differ between treatments. Peak MNTs occurred at 60&#x2009;min for both LDM (16.2&#xa0;N) and HDM (25.0&#xa0;N) treatments. MNTs after HDM treatment were higher than saline (p&#xa0;<&#x2009;0.04) at 15, 60, 90, 120, 150, 180, 240, and 300&#x2009;min post-injection. MNTs after LDM treatment were higher than baseline (p&#xa0;<&#x2009;0.05) at 45 and 60&#x2009;min post-injection. Terminal half-life for HDM was (mean&#x2009;&#xb1;&#x2009;SD) 51.0&#xa0;&#xb1;&#x2009;10.7&#xa0;min, the volume of distribution at steady-state 2.07&#x2009;&#xb1;&#x2009;0.33&#x2009;L/min and clearance 49.2&#xa0;&#xb1;&#x2009;4.16&#x2009;ml * min/kg using noncompartmental analysis. The concentration of morphine-3-glucuronide (M3G) was higher than morphine-6-glucuronide (M6G) at all sampled time points. MAIN LIMITATIONS: Short duration of plasma sampling for pharmacokinetic analysis; lack of objective measure of gastrointestinal function. CONCLUSIONS: The HDM treatment provided mechanical antinociception in donkeys with no significant adverse effects.