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Rapid screening for polymorphisms in dextromethorphan and mephenytoin metabolism.
Author(s) -
Guttendorf RJ,
Britto M,
Blouin RA,
Foster TS,
John W,
Pittman KA,
Wedlund PJ
Publication year - 1990
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1990.tb03653.x
Subject(s) - dextromethorphan , mephenytoin , pharmacology , cyp2d6 , dextrorphan , cyp2c19 , pharmacogenetics , drug interaction , medicine , chemistry , pharmacokinetics , metabolism , cytochrome p450 , biochemistry , genotype , gene
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.