Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon). (25th June 2014)

• Record Type: Journal Article
• Authors: Scala, Christopher; Marsot, Amélie; Limoges, Marie‐Josée; Locatelli, Yann; Simon, Nicolas; Alvarez, Jean‐Claude
• Is Part Of: Veterinary anaesthesia and analgesia. Volume 42:Number 2(2015:Mar.)
• Page Start: 165
• Page End: 172
• Publication Date: 2014-06-25
• Subjects: Veterinary anesthesia -- Periodicals; 636.089
• DOI: 10.1111/vaa.12186
• Languages: English
• ISSNs: 1467-2987

Abstract

<abstract abstract-type="main" id="vaa12186-abs-0001"> <title>Abstract</title> <sec id="vaa12186-sec-0001" sec-type="section"> <title>Objective</title> <p>To assess the population pharmacokinetics of methadone in deer.</p> </sec> <sec id="vaa12186-sec-0002" sec-type="section"> <title>Study design</title> <p>Prospective non‐randomized experimental trial.</p> </sec> <sec id="vaa12186-sec-0003" sec-type="section"> <title>Animals</title> <p>Twelve healthy adult sika deer (nine males and three females).</p> </sec> <sec id="vaa12186-sec-0004" sec-type="section"> <title>Methods</title> <p>Deer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg<sup>−1</sup> or 1 mg kg<sup>−1</sup>. 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).</p> </sec> <sec id="vaa12186-sec-0005" sec-type="section"> <title>Results</title> <p>A 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<sup>−1</sup>), metabolic clearance (34.6 L hour<sup>−1</sup>), 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<sup>−1</sup>), 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<sup>−1</sup>, 121.0 L hour <sup>−1</sup>, 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.</p> </sec> <sec id="vaa12186-sec-0006" sec-type="section"> <title>Conclusions and Clinical relevance</title> <p>Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half‐life in sika deer.</p> </sec> </abstract>