title: Rapid screening for polymorphisms in dextromethorphan and mephenytoin metabolism.
abstract: 1. The phenotyping parameters for dextromethorphan and mephenytoin were assessed in 48 normal male volunteers following administration of each metabolic probe drug on separate occasions and together according to a randomized 3-way crossover design. 2. Neither the urinary S-/R-mephenytoin ratio nor the dextromethorphan metabolic ratio were altered significantly by coadministration of the probe drugs. 3. Five-hundred and nineteen subjects were screened for expression of mephenytoin 4-hydroxylase and dextromethorphan O-demethylase activity following the coadministration of mephenytoin and dextromethorphan. The activity was determined in each case by methods not requiring any quantitative measurements. 4. Nineteen (3.7%) of the subjects were identified as poor metabolizers (PMs) of mephenytoin and 35 subjects (6.7%) as PMs of dextromethorphan. 5. All PMs of dextromethorphan were confirmed by more rigorous evaluation of the metabolic ratio.
authors.affiliation: College of Pharmacy, University of Kentucky, Lexington 40536.
authors.forename: R J
authors.initials: RJ
authors.lastname: Guttendorf
authors.forename: M
authors.initials: M
authors.lastname: Britto
authors.forename: R A
authors.initials: RA
authors.lastname: Blouin
authors.forename: T S
authors.initials: TS
authors.lastname: Foster
authors.forename: W
authors.initials: W
authors.lastname: John
authors.forename: K A
authors.initials: KA
authors.lastname: Pittman
authors.forename: P J
authors.initials: PJ
authors.lastname: Wedlund
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003915:Dextromethorphan / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D006827:Hydantoins / Q000378:metabolism*; D007981:Levorphanol / Q000031:analogs & derivatives*; D008297:Male; D008617:Mephenytoin / Q000378:metabolism*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010084:Oxidation-Reduction; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D006827:Hydantoins; D007981:Levorphanol; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D008617:Mephenytoin