Morphine in donkeys: Antinociceptive effect and preliminary pharmacokinetics.

Abstract

Morphine is the prototypical μ-opioid receptor agonist used to provide analgesia in veterinary species. Its effects are well-described in horses but not donkeys. To determine the antinociceptive effects of two doses of morphine in donkeys. To describe preliminary pharmacokinetic parameters of morphine in donkeys. In vivo experiment. Eight adult castrated male donkeys were given intravenous (IV) 0.9% saline, morphine 0.1mg/kg bwt (LDM), or morphine 0.5mg/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 min post-injection. Venous blood samples were collected pre-injection and 2, 5, 10, 15, 30, 45, 60, 90, and 120 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. Baseline MNT was [median (interquartile range)] 8.9 (7.1-10.3) N and did not differ between treatments. Peak MNTs occurred at 60 min for both LDM (16.2N) and HDM (25.0N) treatments. MNTs after HDM treatment were higher than saline (p< 0.04) at 15, 60, 90, 120, 150, 180, 240, and 300 min post-injection. MNTs after LDM treatment were higher than baseline (p< 0.05) at 45 and 60 min post-injection. Terminal half-life for HDM was (mean ± SD) 51.0± 10.7min, the volume of distribution at steady-state 2.07 ± 0.33 L/min and clearance 49.2± 4.16 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. Short duration of plasma sampling for pharmacokinetic analysis; lack of objective measure of gastrointestinal function. The HDM treatment provided mechanical antinociception in donkeys with no significant adverse effects.