Methadone Disposition: Implementing Lessons Learned.
Methadone Disposition: Implementing Lessons Learned.
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美沙酮处置：吸取经验教训。
DOI：
10.1002/jcph.1427
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发表时间：
2019
影响因子：
2.9
通讯作者：
Greenblatt,DavidJ
中科院分区：
文献类型：
--
作者：
Kharasch,EvanD;Greenblatt,DavidJ
美沙酮是当代治疗药物中研究最深入、但一直被误解的药物之一。它于 1930 年代首次合成，并于 1947 年获得美国食品和药物管理局 (FDA) 批准用于镇痛和镇咳用途。 1 随后在 1960 年代中期，它被证明可以有效治疗阿片成瘾，并于 1972 年获得 FDA 批准用于此用途。美沙酮可有效治疗急性和慢性疼痛，由于作用持续时间长，在当代麻醉实践中越来越多地使用2，是治疗阿片类药物成瘾的两大支柱之一，也是预防艾滋病毒/艾滋病的主要策略。在所有批准的阿片类镇痛药中，美沙酮的作用持续时间最长。它用于婴儿、儿童和成人，通过口服、静脉注射和其他肠胃外途径给药。美沙酮已列入世界卫生组织基本药物清单。美沙酮的开发和批准早在监管机构要求全面的药代动力学特征以及当今药物批准所需的大量体外和体内临床前和临床研究之前就已开发和批准。因此，调查人员在二十多年前就开始填补缺失的信息。对美沙酮代谢进行反应表型分析，以确定负责的 CYP，并进行药物间相互作用研究，以实现机制发现和实际临床考虑。有关美沙酮处置的数据、概念和证据随之发生了巨大的变化。然而，最初的概念和迅速采用的早期“常识”，以及后来被证明是不正确的从业指南和监管文件，一直非常抵制变革。
Methadone is one of the most intensively studied and persistently misunderstood drugs in the contemporary therapeutic armamentarium. First synthesized in the 1930’s, it was approved by the Food and Drug Administration (FDA) in 1947 for analgesic and antitussive use. 1 Subsequently in the mid 1960’s it was shown to be effective in treating opiate addiction, and thence approved by FDA in 1972 for this use. Methadone is effective in treating acute and chronic pain, increasingly used in contemporary anesthesia practice owing to the long duration of effect, 2 is one of the two mainstays in treating opioid addiction, and is a major strategy for HIV/AIDS prevention. Methadone has the longest duration of effect of any approved opioid analgesic. It is used in infants, children, and adults, and is administered by oral, intravenous and other parenteral routes. Methadone is on the World Health Organization List of Essential Medicines.Methadone was developed and approved long before the regulatory requirements for thorough pharmacokinetic characterizations and myriad in vitro and in vivo preclinical and clinical studies which are required today for drug approvals. Hence investigators, more than two decades ago, began to fill in the missing information. There was reaction phenotyping of methadone metabolism to identify responsible CYPs, and drug-drug interaction studies for both mechanistic discovery and practical clinical considerations. The ensuing evolution of data, concepts, and evidence regarding methadone disposition has been vast. Nevertheless however, initial concepts and quickly adopted early “common knowledge”, as well as practitioner guidelines and regulatory documents, which were later shown to be incorrect, have been remarkably resistant to change.