Linked Life Data

12172336

Source:http://linkedlifedata.com/resource/pubmed/id/12172336

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-8-12
pubmed:abstractText
We investigated the effect of the CYP2C19 and CYP2D6 genotypes on the metabolism of amitriptyline (AT) in Japanese psychiatric patients. Steady-state concentrations of AT and its metabolites (nortriptyline [NT], trans-10-hydroxy-nortriptyline [EHNT], cis-10-hydroxy-nortriptyline [ZHNT], trans-10-hydroxy-amitriptyline [EHAT], and cis-10-hydroxy-amitriptyline [ZHAT]) in 50 patients were determined by high-performance liquid chromatography. Significantly higher plasma concentrations of AT corrected for dose and body weight in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 were observed (no mutated alleles vs. two mutated alleles: 36.0 +/- 18.2 vs. 64.0 +/- 25.2 ng/mL/mg/kg, p = 0.025). A significantly higher AT/NT ratio was seen in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 (no mutated alleles vs. two mutated alleles: 1.27 +/- 0.59 vs. 3.40 +/- 1.02, p = 0.001). A trend for higher NT/EHNT ratio in the subjects with two mutated alleles of CYP2D6 than in those with no mutated alleles of CYP2D6 was observed (no mutated alleles vs. two mutated alleles: 0.73 +/- 0.39 vs. 1.31 +/- 0.81, p = 0.068). A trend for higher plasma concentrations of total hydroxylated metabolites of AT (EHAT + ZHAT) corrected for dose and body weight in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 was found (no mutated alleles vs. two mutated alleles: 9.5 +/- 5.8 vs. 17.8 +/- 8.9, p = 0.051). Therefore, the genotype of CYP2C19 is one of the important determinants of the plasma concentrations of AT and the capacity to desmethylate AT. Mother compound AT is shunted via hydroxylation pathways from AT to EHAT and ZHAT in the subjects with homozygotes of mutated alleles of CYP2C19 in order to compensate for the decreased capacity to desmethylate AT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0271-0749
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
371-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12172336-Adolescent, pubmed-meshheading:12172336-Adult, pubmed-meshheading:12172336-Aged, pubmed-meshheading:12172336-Alleles, pubmed-meshheading:12172336-Amitriptyline, pubmed-meshheading:12172336-Antidepressive Agents, Tricyclic, pubmed-meshheading:12172336-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:12172336-Cytochrome P-450 CYP2D6, pubmed-meshheading:12172336-Cytochrome P-450 Enzyme System, pubmed-meshheading:12172336-Female, pubmed-meshheading:12172336-Genotype, pubmed-meshheading:12172336-Humans, pubmed-meshheading:12172336-Japan, pubmed-meshheading:12172336-Male, pubmed-meshheading:12172336-Mental Disorders, pubmed-meshheading:12172336-Middle Aged, pubmed-meshheading:12172336-Mixed Function Oxygenases, pubmed-meshheading:12172336-Mutation, pubmed-meshheading:12172336-Regression Analysis
pubmed:year
2002
pubmed:articleTitle
The impact of CYP2C19 and CYP2D6 genotypes on metabolism of amitriptyline in Japanese psychiatric patients.
pubmed:affiliation
Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan. shimoda@belle.shiga-med.ac.jp
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't