DEXTROMETHORPHAN METABOLISM IN JORDANIANS - DISSOCIATION OF DEXTROMETHORPHAN O-DEMETHYLATION FROM DEBRISOQUINE 4-HYDROXYLATION

The concentrations of dextromethorphan (DM) and its metabolites dextro rphan (DRP), 3-methoxymorphinan (MM) and 3-hydroxymorphinan (HM) were measured in 8 h urine samples from 266 unrelated healthy Jordanian sub jects following oral administration of 30 mg dextromethorphan hydrobro mide and using a rapid, sensitive and precise HPLC method with fluorom etric detection. The frequency of the 'poor' metabolizer status of DM- O-demethylation as judged by log DM/DRP was found to be 6.8% with a 95 % confidence interval of 3.8-9.8%. There was a strong correlation betw een log DM/DRP and log total non-O-demethylated compounds (NODM)/total O-demethylated metabolites (ODM) metabolic ratios (r = 0.96, P < 0.01 ). However, one subject with log DM/DRP of 0.05 that classifies him as a poor metabolizer was found to have a log NODM/ODM of -0.73 which is in the range of extensive metabolizer status suggesting the presence of another cytochrome P450 isoenzyme involved in dextromethorphan O-de methylation. Dextromethorphan N-demethylation to 3-methoxymorphinan wa s detected in 55.3% of individuals. Furthermore, a dissociation betwee n dextromethorphan O-demethylation and debrisoquine (D) 4-hydroxylatio n has been observed. Among the 116 subjects phenotyped with both dextr omethorphan and debrisoquine, 7 were poor metabolizers of both, three were poor metabolizers of debrisoquine and extensive metabolizers of d extromethorphan whilst 4 were poor metabolizers of dextromethorphan an d extensive metabolizers of debrisoquine, one of whom was reclassified as an extensive metabolizer of dextromethorphan using log NODM/ODM to characterize dextromethorphan metabolizer status.