Chi Won Shin, Heather Knych, Isabelle Desprez, Barbara Ambros
{"title":"家养雪貂(Mustela putorius furo)静脉注射和皮下注射美沙酮的药代动力学。","authors":"Chi Won Shin, Heather Knych, Isabelle Desprez, Barbara Ambros","doi":"10.1016/j.vaa.2024.08.009","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To determine the pharmacokinetic profile of methadone after intravenous (IV) and subcutaneous (SC) administration in domestic ferrets (Mustela putorius furo).</p><p><strong>Study design: </strong>Crossover experimental study.</p><p><strong>Animals: </strong>A group of eight healthy adult ferrets weighing 1.01 ± 0.23 kg (mean ± standard deviation).</p><p><strong>Methods: </strong>Methadone hydrochloride (0.3 mg kg<sup>-1</sup>) was injected IV or SC to each ferret with a 3 week washout period. Blood samples were collected via a jugular catheter before and 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360 and 480 minutes after drug administration. Liquid chromatography-tandem mass spectrometry was used to determine plasma methadone concentrations. A nonlinear mixed effects model was used to analyze the data.</p><p><strong>Results: </strong>After IV injection, systemic clearance (Cl<sub>ss</sub>) and volume of distribution (Vd<sub>ss</sub>) were 78.9 mL min<sup>-1</sup> kg<sup>-1</sup> and 9.8 L kg<sup>-1</sup>, respectively. Elimination half-life was 2.0 hours and SC bioavailability was fixed at 1. The maximum observed plasma concentration after SC injection was 92.1 ± 76.8 ng mL<sup>-1</sup>. Behavioral changes were observed after both routes.</p><p><strong>Conclusions and clinical relevance: </strong>The pharmacokinetic profile of IV methadone was characterized by a high Cl<sub>ss</sub> and large Vd<sub>ss</sub>, with high bioavailability and absorption rate after SC administration. Half-life was short and mean plasma methadone concentrations stayed above the minimum effective concentration (MEC) reported in humans only after SC administration for 5 minutes, but remained above that reported in dogs for 45 minutes following both routes. Further studies investigating the MEC and pharmacodynamics of methadone in ferrets are warranted.</p>","PeriodicalId":23626,"journal":{"name":"Veterinary anaesthesia and analgesia","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics of methadone after intravenous and subcutaneous administration in domestic ferrets (Mustela putorius furo).\",\"authors\":\"Chi Won Shin, Heather Knych, Isabelle Desprez, Barbara Ambros\",\"doi\":\"10.1016/j.vaa.2024.08.009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To determine the pharmacokinetic profile of methadone after intravenous (IV) and subcutaneous (SC) administration in domestic ferrets (Mustela putorius furo).</p><p><strong>Study design: </strong>Crossover experimental study.</p><p><strong>Animals: </strong>A group of eight healthy adult ferrets weighing 1.01 ± 0.23 kg (mean ± standard deviation).</p><p><strong>Methods: </strong>Methadone hydrochloride (0.3 mg kg<sup>-1</sup>) was injected IV or SC to each ferret with a 3 week washout period. Blood samples were collected via a jugular catheter before and 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360 and 480 minutes after drug administration. Liquid chromatography-tandem mass spectrometry was used to determine plasma methadone concentrations. A nonlinear mixed effects model was used to analyze the data.</p><p><strong>Results: </strong>After IV injection, systemic clearance (Cl<sub>ss</sub>) and volume of distribution (Vd<sub>ss</sub>) were 78.9 mL min<sup>-1</sup> kg<sup>-1</sup> and 9.8 L kg<sup>-1</sup>, respectively. Elimination half-life was 2.0 hours and SC bioavailability was fixed at 1. The maximum observed plasma concentration after SC injection was 92.1 ± 76.8 ng mL<sup>-1</sup>. Behavioral changes were observed after both routes.</p><p><strong>Conclusions and clinical relevance: </strong>The pharmacokinetic profile of IV methadone was characterized by a high Cl<sub>ss</sub> and large Vd<sub>ss</sub>, with high bioavailability and absorption rate after SC administration. Half-life was short and mean plasma methadone concentrations stayed above the minimum effective concentration (MEC) reported in humans only after SC administration for 5 minutes, but remained above that reported in dogs for 45 minutes following both routes. Further studies investigating the MEC and pharmacodynamics of methadone in ferrets are warranted.</p>\",\"PeriodicalId\":23626,\"journal\":{\"name\":\"Veterinary anaesthesia and analgesia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-09-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Veterinary anaesthesia and analgesia\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1016/j.vaa.2024.08.009\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary anaesthesia and analgesia","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1016/j.vaa.2024.08.009","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
Pharmacokinetics of methadone after intravenous and subcutaneous administration in domestic ferrets (Mustela putorius furo).
Objective: To determine the pharmacokinetic profile of methadone after intravenous (IV) and subcutaneous (SC) administration in domestic ferrets (Mustela putorius furo).
Study design: Crossover experimental study.
Animals: A group of eight healthy adult ferrets weighing 1.01 ± 0.23 kg (mean ± standard deviation).
Methods: Methadone hydrochloride (0.3 mg kg-1) was injected IV or SC to each ferret with a 3 week washout period. Blood samples were collected via a jugular catheter before and 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360 and 480 minutes after drug administration. Liquid chromatography-tandem mass spectrometry was used to determine plasma methadone concentrations. A nonlinear mixed effects model was used to analyze the data.
Results: After IV injection, systemic clearance (Clss) and volume of distribution (Vdss) were 78.9 mL min-1 kg-1 and 9.8 L kg-1, respectively. Elimination half-life was 2.0 hours and SC bioavailability was fixed at 1. The maximum observed plasma concentration after SC injection was 92.1 ± 76.8 ng mL-1. Behavioral changes were observed after both routes.
Conclusions and clinical relevance: The pharmacokinetic profile of IV methadone was characterized by a high Clss and large Vdss, with high bioavailability and absorption rate after SC administration. Half-life was short and mean plasma methadone concentrations stayed above the minimum effective concentration (MEC) reported in humans only after SC administration for 5 minutes, but remained above that reported in dogs for 45 minutes following both routes. Further studies investigating the MEC and pharmacodynamics of methadone in ferrets are warranted.
期刊介绍:
Veterinary Anaesthesia and Analgesia is the official journal of the Association of Veterinary Anaesthetists, the American College of Veterinary Anesthesia and Analgesia and the European College of Veterinary Anaesthesia and Analgesia. Its purpose is the publication of original, peer reviewed articles covering all branches of anaesthesia and the relief of pain in animals. Articles concerned with the following subjects related to anaesthesia and analgesia are also welcome:
the basic sciences;
pathophysiology of disease as it relates to anaesthetic management
equipment
intensive care
chemical restraint of animals including laboratory animals, wildlife and exotic animals
welfare issues associated with pain and distress
education in veterinary anaesthesia and analgesia.
Review articles, special articles, and historical notes will also be published, along with editorials, case reports in the form of letters to the editor, and book reviews. There is also an active correspondence section.