Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-4-19
pubmed:abstractText
The polymorphism of dextromethorphan (CAS 125-71-3) metabolism is dependent on hepatic cytochrom P4502D6 (CYP2D6) activity. The relationship between the CYP2D6 genotype and the dextromethorphan phenotype was studied in 83 healthy unrelated subjects. Genotype was determined by allele-specific polymerase chain reaction (PCR). Phenotyping was performed by administration of 25 mg dextromethorphan hydrobromide and determination of the urinary metabolic ratio of dextromethorphan and its O-demethylated metabolite dextrorphan (DEM/DOR). Six subjects (7.2%) were homozygous for mutant alleles (95% confidence interval 2.7%-14.7%), 18 subjects (22%) were heterozygous carriers, and 59 were homozygous for the wild-type allele. Six subjects were classified as poor metabolizers (PM) of dextromethorphan, 77 as extensive metabolizers (EM). Genotyping correctly predicted all PMs and EMs. The CYP2D6-B mutation was most frequently found, being present in 83% of PM and 8% of EM alleles. Heterozygous EMs (22% of the total population studied) were significantly underrepresented compared to the expected genotype frequency of 31% (p < 0.05). The extensive metabolizers who were heterozygous for the wild-type allele had a significantly higher metabolic ratio, compared to the homozygous EMs (log10DEM/DOR [95% = -1.99 [(-2.30)-(-1.69)] vs. -2.55 [(-2.67)-(-2.43)]; p < 0.001), indicating a gene-dose effect for CYP2D6.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0004-4172
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-3
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Prediction of phenotype for dextromethorphan O-demethylation by using polymerase chain reaction in healthy volunteers.
pubmed:affiliation
Forschung und Entwicklung, Pfizer/Mack, Illertissen, Fed. Rep. of Germany.
pubmed:publicationType
Journal Article, Clinical Trial