Cytochrome P-450IID6 phenotyping in cancer patients: debrisoquin and dextromethorphan as probes.
The usefulness of substituting dextromethorphan for debrisoquin as a probe for cytochrome P-450IID6 deficiency was investigated in 20 male cancer patients. Each patient was studied on two occasions. An oral dose of dextromethorphan (60 mg) was administered to 13 patients and are week later an oral dose of debrisoquin (10 mg) was administered to each patient. The order was reversed for the other 7 patients. An 8-h urine sample was collected after administration of each test drug and assayed for parent drug and metabolites. Five poor metabolizers (PMs) and 15 extensive metabolizers (EMs) of debrisoquin were tested. The debrisoquin metabolic ratio (DMR), calculated as [parent drug]/[metabolite], correlated with the metabolic ratio of dextromethorphan (R2 = 0.58, P = 0.0001). All PMs of debrisoquin (metabolic ratio > 12.0) were easily identified as being PMs of dextromethorphan (metabolic ratio > 0.30). Within the EM group, there was a significant correlation between the metabolic ratios of debrisoquin and dextromethorphan (R2 = 0.82, P < 0.0001). There was not as clear a correlation in the PM group (R2 = 0.32, P = 0.32). These findings suggest that dextromethorphan can be substituted for debrisoquin in establishing the debrisoquin phenotype in a patient population with metastatic cancer.
Anthony
L B
LB
Division of Medical Oncology, Vanderbilt Clinic, Nashville, TN 37232-5536, USA.
Boeve
T J
TJ
Hande
K R
KR
D000368:Aged; D002849:Chromatography, Gas / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003647:Debrisoquin / Q000378:metabolism*; D003915:Dextromethorphan / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D010641:Phenotype; D012044:Regression Analysis; D012680:Sensitivity and Specificity
D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin