Increasing plasma methadone concentrations are associated with decreased leukocyte oxidative burst without affecting cytokine production or phagocytosis in healthy dogs.

Abstract

Objective: To determine whether methadone administration affects leukocyte phagocytic function, oxidative burst, and cytokine production and if immune function is associated with plasma methadone concentrations in dogs.

Methods: This was a prospective, randomized, placebo-controlled, nonblinded crossover study. Ten client-owned healthy dogs were included in the 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 interval period. Blood was collected at baseline (ie, before treatment administration) and then 10 minutes, 6 hours, and 24 hours after the first treatment administration. Immune function tests and plasma methadone concentrations were measured at all time points (before treatment administration and 10 minutes, 6 hours, and 24 hours after the first treatment administration). Plasma methadone concentrations were measured with liquid chromatography quadrupole time-of-flight mass spectrometry. Whole blood cultures were performed with exposure to PBS, lipopolysaccharide, and lipoteichoic acid. Canine-specific multiplex assay was used to measure tumor necrosis factor-α, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor concentrations in the supernatant. Granulocytic and monocytic phagocytosis and oxidative burst were evaluated via flow cytometry.

Results: There was a moderate inverse association between the percentage of granulocytes and monocytes undergoing oxidative burst and plasma methadone concentrations (r = -0.88, r2 = 0.77, P < .001). Oxidative burst percentage increased over time regardless of treatment (F[1,67] = 7.758; P < .007). No other between treatment or time differences were identified.

Conclusions: Increasing methadone concentrations is associated with decreased leukocyte oxidative burst in healthy dogs.

Clinical relevance: Methadone may have immunologic effects in dogs but requires additional investigation.