Dextromethorphan to dextrorphan urinary metabolic ratio does not reflect dextromethorphan oral clearance

Silvana Borges, Lang Li, Mitchell A. Hamman, David R. Jones, Stephen D. Hall, J. Christopher Gorski

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Dextromethorphan urinary metabolic ratio is widely used to determine the CYP2D6 phenotype, but its utility to reflect subtle differences in catalytic activity is unclear. We evaluated the capability of dextromethorphan urinary metabolic ratio to predict dextromethorphan oral clearance as a measure of CYP2D6 activity. Data from 10 healthy extensive metabolizers of CYP2D6 were given 30 mg of dextromethorphan hydrobromide orally on two occasions. Blood and urine samples were collected for 72 h. Dextromethorphan and dextrorphan were determined in urine by high-performance liquid chromatography with fluorescence detection and in serum by liquid chromatography-mass spectrometry. The urinary metabolic ratio was very weakly correlated with dextromethorphan oral clearance (r = 0.24; p = 0.04). In contrast, the dextromethorphan oral clearance was highly correlated with the dextromethorphan to dextrorphan area under the concentration-time curve ratio (r = 0.84; p = 0.005) and the 3-h (r = 0.60; p = 0.003), 4-h (r = 0.72, p ≤ 0.001), 6-h (r = 0.67; p ≤ 0.001), and 8-h (r = 0.74; p ≤ 0.001) dextromethorphan to dextrorphan serum ratios. Assuming an effect size of 30%, the number of volunteers required for crossover and cross-sectional studies using the urinary metabolic ratio as the CYP2D6 index was calculated to be 56 and 524, respectively, whereas 14 and 60 subjects are needed if oral clearance is used. Considering the required sample size and the low correlation with oral clearance, urinary metabolic ratio is not recommended as the primary outcome variable in studies requiring the detection of modest changes in CYP2D6 activity.

Original languageEnglish
Pages (from-to)1052-1055
Number of pages4
JournalDrug Metabolism and Disposition
Volume33
Issue number7
DOIs
StatePublished - Jul 2005

Fingerprint

Dextrorphan
Dextromethorphan
Cytochrome P-450 CYP2D6
Urine
Liquid chromatography
High performance liquid chromatography
Serum
Liquid Chromatography
Sample Size
Mass spectrometry
Volunteers
Catalyst activity
Mass Spectrometry
Blood
Cross-Sectional Studies
Fluorescence
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Borges, S., Li, L., Hamman, M. A., Jones, D. R., Hall, S. D., & Christopher Gorski, J. (2005). Dextromethorphan to dextrorphan urinary metabolic ratio does not reflect dextromethorphan oral clearance. Drug Metabolism and Disposition, 33(7), 1052-1055. https://doi.org/10.1124/dmd.104.003459

Dextromethorphan to dextrorphan urinary metabolic ratio does not reflect dextromethorphan oral clearance. / Borges, Silvana; Li, Lang; Hamman, Mitchell A.; Jones, David R.; Hall, Stephen D.; Christopher Gorski, J.

In: Drug Metabolism and Disposition, Vol. 33, No. 7, 07.2005, p. 1052-1055.

Research output: Contribution to journalArticle

Borges, S, Li, L, Hamman, MA, Jones, DR, Hall, SD & Christopher Gorski, J 2005, 'Dextromethorphan to dextrorphan urinary metabolic ratio does not reflect dextromethorphan oral clearance', Drug Metabolism and Disposition, vol. 33, no. 7, pp. 1052-1055. https://doi.org/10.1124/dmd.104.003459
Borges, Silvana ; Li, Lang ; Hamman, Mitchell A. ; Jones, David R. ; Hall, Stephen D. ; Christopher Gorski, J. / Dextromethorphan to dextrorphan urinary metabolic ratio does not reflect dextromethorphan oral clearance. In: Drug Metabolism and Disposition. 2005 ; Vol. 33, No. 7. pp. 1052-1055.
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