Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal.
Department of Sciences, IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal.
Drug Metab Rev. 2020 May;52(2):258-282. doi: 10.1080/03602532.2020.1758712. Epub 2020 May 12.
Dextromethorphan (DXM) is a safe and effective antitussive agent present in several over the counter cough and cold medications. At higher doses, it causes psychoactive effects, making it appealing for abuse. In this work, the pharmacokinetics and pharmacodynamics of DXM with clinical and forensic relevance were extensively reviewed. DXM and related known metabolizing enzymes and metabolites were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Major metabolic pathways include sequential -demethylation and -demethylation of DXM, yielding dextrorphan (DXO), the major active metabolite, and 3-hydroxymorphinan, the bi-demethylated product, respectively. The demethylation order described may reverse being the resultant mid product 3-methoxymorphinan. UDP-glucuronosyltranferase produces glucuronide conjugates. Genotypic variations in enzymes and interactions with other drugs can result in large inter-individual variability in the pharmacological and toxicological effects produced. Knowing the metabolism of DXM may help to better understand the inter-individual variability in the pharmacokinetics and pharmacodynamics and to avoid adverse effects.
右美沙芬（DXM）是一种安全有效的镇咳药，存在于几种非处方咳嗽和感冒药中。在较高剂量下，它会产生精神活性作用，因此很容易被滥用。在这项工作中，广泛综述了与临床和法医学相关的 DXM 的药代动力学和药效学。在书籍和 PubMed（美国国家医学图书馆）中搜索 DXM 和相关已知的代谢酶和代谢物，没有时间限制。主要代谢途径包括 DXM 的顺序去甲基化和去甲基化，分别生成主要的活性代谢物右美沙芬（DXO）和双去甲基产物 3-羟吗啡烷。所描述的去甲基化顺序可能会逆转，成为中间产物 3-甲氧基吗啡烷。UDP-葡萄糖醛酸转移酶产生葡萄糖醛酸缀合物。酶的基因型变异和与其他药物的相互作用可能导致药物代谢动力学和药效学产生的个体间变异性很大。了解 DXM 的代谢可能有助于更好地理解个体间变异性在药代动力学和药效学中的作用，并避免不良反应。
