title: Phenotyping polymorphic drug metabolism in the French Caucasian population.
abstract: Because of the large interethnic differences in the incidence of poor metabolizer phenotypes, French Caucasians have been studied for two independent polymorphisms, debrisoquine/dextromethorphan and mephenytoin metabolism. One hundred and thirty-two unrelated French Caucasians were phenotyped using oral doses of dextromethorphan 20 mg and mephenytoin 100 mg. Individual dextrorphan excretion over 8 h and the dextromethorphan/dextrorphan metabolic ratio were calculated. Extensive metabolizers were taken as subjects with a high dextrorphan output (15.56 mumol/8 h) and a low metabolic ratio (0.0023), and poor metabolizers were those with a low dextrorphan output (0.39 mumol/8 h) and a high metabolic ratio (7.00). Individual 4-hydroxymephenytoin excretion and mephenytoin hydroxylation indices were also determined. Extensive metabolizers eliminated large amounts of 4 hydroxymephenytoin (133.2 mumol/8 h) and had a hydroxylation index of 1.99, and poor metabolizers, because of impaired mephenytoin metabolism, had a high hydroxylation index (277). The incidence of the poor metabolizer phenotype was 3% for dextromethorphan (95% confidence limits 0.5%-8.5%) and 6% for mephenytoin (95% confidence limits 2%-12.5%).
authors.affiliation: INSERM Unité 120, Le Vésinet, France.
authors.forename: E
authors.initials: E
authors.lastname: Jacqz
authors.forename: H
authors.initials: H
authors.lastname: Dulac
authors.forename: H
authors.initials: H
authors.lastname: Mathieu
mesh_terms: D000328:Adult; D003915:Dextromethorphan / Q000378:metabolism*; D005260:Female; D005602:France; D006801:Humans; D006827:Hydantoins / Q000378:metabolism*; D007981:Levorphanol / Q000031:analogs & derivatives*; D008297:Male; D008617:Mephenytoin / Q000031:analogs & derivatives / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D044465:White People
chemical_list: D006827:Hydantoins; D007981:Levorphanol; C025687:4-hydroxymephenytoin; D003915:Dextromethorphan; D008617:Mephenytoin