Mephenytoin and sparteine pharmacogenetics in Canadian Caucasians.
The frequency of genetically deficient hydroxylation of mephenytoin (M-defect) was studied in 83 healthy Caucasians living in Toronto. The M-defect was compared with the widely studied genetic polymorphism of sparteine/debrisoquine oxidations (S-defect). After ingestion of mephenytoin and sparteine, urine samples (0 to 24 hr) were analyzed for p(4')-hydroxymephenytoin and urine samples over 0 to 12 hr were analyzed for sparteine and 2-and 5-dehydrosparteine by gas chromatographic methods. Nirvanol, the N-demethylation product of mephenytoin, was determined by a newly developed gas chromatographic/mass spectrometric method. Frequency distributions of both p-hydroxymephenytoin and dehydrosparteine excreted in urine were discontinuous (bimodal), while nirvanol and sparteine data were normally distributed. Two poor metabolizers of mephenytoin excreted 2% to 3% of the dose as p-hydroxymephenytoin and excreted normal amounts of nirvanol, but they were extensive metabolizers of sparteine. Six poor metabolizers of sparteine were found to be extensive metabolizers of mephenytoin (34% to 42% excreted in urine as p-hydroxyme-phenytoin). Thus the M-defect occurs among Canadian Caucasians with a frequency of 2% (0.0% to 7.5% with a confidence limit of 99%) and is independent of the S-defect.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006827:Hydantoins / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D008617:Mephenytoin / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D010597:Pharmacogenetics; D013034:Sparteine / Q000378:metabolism* / Q000652:urine; D044465:White People
D006827:Hydantoins; D013034:Sparteine; D008617:Mephenytoin