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 meta bolic ratios from six different dextromethorphan phenotyping doses to ascer tain whether Linearity existed over a dosage range. Forty subjects were enr olled 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 crossove r fashion. Urinary dextromethorphan to dextrorphan molar ratios were used t o measure CYP2D6 activity. Single blood samples were obtained for CYP2D6 ge notyping, 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 dextromethorp han for phenotyping to avoid dose dependency.