Background: Methadone is a commonly used opioid in dogs, though its immunological effects are poorly characterized.
Objectives: Determine whether methadone administration affects leukocyte phagocytic function, oxidative burst, and cytokine production and if immune function is associated with plasma methadone concentrations. Animals: Ten owned healthy dogs.
Methods: Prospective randomized, placebo-controlled, open-label, cross-over study. Dogs were randomized to receive either methadone (0.3 mg/kg, IV) or placebo (0.9% NaCl, IV) once every 6 hours for 24 hours. Dogs were crossed over to the alternative treatment following a 7-day washout period. Blood was collected at baseline (i.e. before treatment administration; T0) and then 10 minutes (T1), 6 hours (T2), and 24 hours (T3) after treatment administration. Immune function tests and plasma methadone concentrations were measured at all time points (T0-T3). Plasma methadone concentrations were measured with liquid chromatography quadrupole time-of-flight mass spectrometry. Whole blood cultures were performed with exposure to PBS, LPS, and LTA. Canine specific multiplex assay was used to measure TNF-α, IL-6, and IL-10 concentrations in supernatant. Granulocytic and monocytic (GM) phagocytosis and oxidative burst were evaluated via flow cytometry with previously validated assays.
Results: There was a moderate inverse association between the percentage of GM undergoing oxidative burst and plasma methadone concentrations (r = - 0.52; 95% CI: - 0.78 to - 0.11; P = 0.02). No time-dependent or between treatment differences in immune function results were identified after adjustments for multiple comparisons (P > 0.05). Conclusions & Clinical Importance: Methadone may have immunologic effects in dogs but requires additional investigation.
