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Dose dependency of dextromethorphan for cytochrome P450 2D6 (CYP2D6) phenotyping
Author(s) -
Streetman Daniel S.,
Ellis Ross E.,
Nafziger Anne N.,
Leeder J. Steven,
Gaedigk Andrea,
Gotschall Russell,
Kearns Gregory L.,
Bertino Joseph S.
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(99)70018-4
Subject(s) - dextromethorphan , dextrorphan , cyp2d6 , pharmacology , medicine , urine , crossover study , cyp2c9 , anesthesia , cytochrome p450 , placebo , metabolism , alternative medicine , pathology
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: