• Christopher Scala, Amélie Marsot, Marie-Josée Limoges, Yann Locatelli, Nicolas Simon, and Jean-Claude Alvarez.
• Réserve de la Haute-Touche, Muséum National d'Histoire Naturelle, Obterre, France.
• Vet Anaesth Analg. 2015 Mar 1;42(2):165-72.

ObjectiveTo assess the population pharmacokinetics of methadone in deer.Study DesignProspective non-randomized experimental trial.AnimalsTwelve healthy adult sika deer (nine males and three females).MethodsDeer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg(-1) or 1 mg kg(-1) . Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM).ResultsA two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour(-1) ), metabolic clearance (34.6 L hour(-1) ), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour(-1) ), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour(-1) , 121.0 L hour (-1) , 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration.Conclusions And Clinical RelevanceFollowing intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer.© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

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