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 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.
Streetman
D S
DS
Clinical Pharmacology Research Center, the Department of Medicine, Bassett Healthcare, Cooperstown, NY 13326-1394, USA.
Ellis
R E
RE
Nafziger
A N
AN
Leeder
J S
JS
Gaedigk
A
A
Gotschall
R
R
Kearns
G L
GL
Bertino
J S
JS
D000328:Adult; D000483:Alleles; D000996:Antitussive Agents / Q000008:administration & dosage; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003915:Dextromethorphan / Q000008:administration & dosage* / Q000009:adverse effects / Q000652:urine; D003917:Dextrorphan / Q000652:urine; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000996:Antitussive Agents; D018691:Excitatory Amino Acid Antagonists; D003917:Dextrorphan; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6