Pharmacokinetics and Pharmacodynamics of Dextromethorphan: Clinical and Forensic Aspects

Abstract

Dextromethorphan (DXM) is a safe and effective antitussive agent present in several over the counter cough and cold medication. At high doses, 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 O-demethylation and N-demethylation of dextromethorphan, yielding dextrorphan, major active metabolite, and 3-hydroxymorphinan, the bi-demethylated product, respectively. The demethylation order described may reverse, being the resultant mid product 3-methoxymorphinan. UDPglucuronosyltranferase forms 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 better understand the inter-individual variability of its pharmacokinetics and pharmacodynamics and avoid adverse effects.