Dose dependency of dextromethorphan for cytochrome P450 2D6 (CYP2D6) phenotyping

Most dextromethorphan CYP2D6 phenotyping studies use a 30‐mg dose, but data that show superiority of any particular dose are lacking. We compared metabolic ratios from six different dextromethorphan phenotyping doses to ascertain whether linearity existed over a dosage range. Forty subjects were enr...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 1999-11, Vol.66 (5), p.535-541
Main Authors: Streetman, Daniel S., Ellis, Ross E., Nafziger, Anne N., Leeder, J. Steven, Gaedigk, Andrea, Gotschall, Russell, Kearns, Gregory L., Bertino, Joseph S.
Format: Article
Language:English
Subjects:
Adult
Alleles
Antitussive Agents - administration & dosage
Biological and medical sciences
Cross-Over Studies
Cytochrome P-450 CYP2D6 - genetics
Dextromethorphan - administration & dosage
Dextromethorphan - adverse effects
Dextromethorphan - urine
Dextrorphan - urine
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists - administration & dosage
Female
Humans
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Phenotype
Respiratory system
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Summary:Most dextromethorphan CYP2D6 phenotyping studies use a 30‐mg dose, but data that show superiority of any particular dose are lacking. We compared metabolic ratios from six different dextromethorphan phenotyping doses to ascertain whether linearity existed over a dosage range. Forty subjects were enrolled in the study. Each subject received 0.05 mg/kg, 0.15 mg/kg, 0.3 mg/kg, 30 mg, 0.8 mg/kg, and 1.2 mg/kg dextromethorphan in a randomized crossover fashion. Urinary dextromethorphan to dextrorphan molar ratios were used to measure CYP2D6 activity. Single blood samples were obtained for CYP2D6 genotyping, which revealed one poor metabolizer and 39 extensive metabolizers. A statistical difference was found for the molar ratio between the 0.8 mg/kg and the 1.2 mg/kg dose compared with the other four doses. None of the 39 genotypic extensive metabolizers were incorrectly phenotyped with any of these doses. These data support the use of moderate doses of dextromethorphan for phenotyping to avoid dose dependency. Clinical Pharmacology & Therapeutics (1999) 66, 535–541; doi:
ISSN:0009-9236
1532-6535
DOI:10.1016/S0009-9236(99)70018-4