Dextromethorphan polymorphic hepatic oxidation (CYP2D6) in healthy black American adult subjects.
The objective of this study was to assign metabolizer phenotype to 107 healthy adult black Americans using dextromethorphan as the substrate probe. Eligible subjects were unrelated, healthy, nonsmoking, aged 18-50 years, and taking no medications. Fifteen milliliters of dextromethorphan syrup (85 mumol, 30 mg) was administered orally at bedtime, and 8-h overnight urine was collected. Dextromethorphan and dextrorphan urinary areas and molar ratios were determined using high-performance liquid chromatography with fluorescence detection. A molar metabolic ratio of < 0.3 was used to segregate poor metabolizers (PM) from extensive metabolizers (EM). Data were obtained in 99 subjects: 68 women, 31 men. (Five were lost to follow-up, three did not take the probe drug.) Six (6.1%) were PM (five women, one man), and 93 were EM. The prevalence of PM was 6.1% (95% confidence interval, 2.3-12.7%) in our sample. This compares to 5 to 10% reported in white unrelated subjects and 1.9% in 106 black children (64 healthy and 42 with cancer), and 0-8.6% in black African populations. The clinical implications of these findings warrant further investigation.
Marinac
J S
JS
Department of Medicine, University of Missouri-Kansas City, School of Medicine 64108, USA.
Foxworth
J W
JW
Willsie
S K
SK
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D044383:Black People; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003915:Dextromethorphan / Q000493:pharmacokinetics* / Q000652:urine; D003917:Dextrorphan / Q000378:metabolism / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D001741:Black or African American
D003917:Dextrorphan; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6