Dextromethorphan: polymorphic serum pattern of the O-demethylated and didemethylated metabolites in man

1. The interindividual differences in serum concentrations of dextromethorphan (DM) and its metabolites were studied in 29 healthy subjects given 120 mg orally. They were also phenotyped according to the urinary ratio of debrisoquine and 4-hydroxy-debrisoquine. 2. Four (14%) subjects were found to be poor metabolizers (PM) with a dextromethorphan/dextrorphan metabolite ratio in plasma of 3.6 or more compared with extensive metabolizers (EM) with a ratio of 0.11 or less. Significant levels of 3-hydroxymorphinan were measurable in all individuals except two, both of whom were PMs. This subdivision corresponded to the phenotype determined by the metabolic ratio of debrisoquine (r = 0.92). 3. Twelve of the 29 subjects reported adverse drug reactions after dextromethorphan administration compared with none after placebo.