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Dextromethorphan metabolism in Jordanians: Dissociation of dextromethorphan O-demethylation from debrisoquine 4-hydroxylation

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Summary

The concentrations of dextromethorphan (DM) and its metabolites dextrorphan (DRP), 3-methoxymorphinan (MM) and 3-hydroxymorphinan (HM) were measured in 8 h urine samples from 266 unrelated healthy Jordanian subjects following oral administration of 30 mg dextromethorphan hydrobromide and using a rapid, sensitive and precise HPLC method with fluorometric 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 between 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-demethylation. Dextromethorphan N-demethylation to 3-methoxymorphinan was detected in 55.3% of individuals. Furthermore, a dissociation between dextromethorphan O-demethylation and debrisoquine (D) 4-hydroxylation has been observed. Among the 116 subjects phenotyped with both dextromethorphan and debrisoquine, 7 were poor metabolizers of both, three were poor metabolizers of debrisoquine and extensive metabolizers of dextromethorphan whilst 4 were poor metabolizers of dextromethorphan and extensive metabolizers of debrisoquine, one of whom was reclassified as an extensive metabolizer of dextromethorphan using log NODM/ODM to characterize dextromethorphan metabolizer status.

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Author notes

  1. A. Latif

    Present address: Department of Internal Medicine, Hamad Medical Establishment, Doha, Qatar

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Alquds University, P.O. Box 20002, Jerusalem

    Y. M. Irshaid

  2. Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan

    H. F. Al-Hadidi, F. Awwadi, M. Al-Zoubi & N. M. Rawashdeh

  3. Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan

    A. Latif

Authors
  1. Y. M. Irshaid
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  2. H. F. Al-Hadidi
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  3. A. Latif
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  4. F. Awwadi
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  5. M. Al-Zoubi
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  6. N. M. Rawashdeh
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Irshaid, Y.M., Al-Hadidi, H.F., Latif, A. et al. Dextromethorphan metabolism in Jordanians: Dissociation of dextromethorphan O-demethylation from debrisoquine 4-hydroxylation. European Journal of Drug Metabolism and Pharmacokinetics 21, 301–307 (1996). https://doi.org/10.1007/BF03189731

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  • DOI: https://doi.org/10.1007/BF03189731

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