Source:http://linkedlifedata.com/resource/pubmed/id/19884907
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2010-5-24
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pubmed:abstractText |
CYP2C19 converts the tricyclic antidepressant imipramine to its active metabolite desipramine, which is subsequently inactivated by CYP2D6. The novel CYP2C19*17 allele causes ultrarapid metabolism of CYP2C19 substrates. We genotyped 178 depressed patients on imipramine for CYP2C19*17, and measured steady-state imipramine and desipramine plasma concentrations. Mean dose-corrected imipramine plasma concentration was significantly dependent on CYP2C19 genotype (Kruskal-Wallis test, P=0.01), with circa 30% lower levels in CYP2C19*17/*17 individuals compared with CYP2C19*1/*1 (wild-type) patients. The mean dose-corrected imipramine+desipramine plasma concentrations and imipramine/desipramine ratios were not significantly different between genotype subgroups (Kruskal-Wallis tests, P>or=0.12). In a multivariate analysis, we found a significant, but limited effect (P=0.035, eta(2)=0.031) of the CYP2C19*17 genotype on imipramine+desipramine concentrations. Although the CYP2C19*17 allele is associated with a significantly increased metabolism of imipramine, CYP2C19*17 genotyping will, in our view, not importantly contribute to dose management of patients on imipramine therapy guided by imipramine+desipramine plasma concentrations.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antidepressive Agents, Tricyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/CYP2C19 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Desipramine,
http://linkedlifedata.com/resource/pubmed/chemical/Imipramine
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1473-1150
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
219-25
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pubmed:meshHeading |
pubmed-meshheading:19884907-Adult,
pubmed-meshheading:19884907-Antidepressive Agents, Tricyclic,
pubmed-meshheading:19884907-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:19884907-Depression,
pubmed-meshheading:19884907-Desipramine,
pubmed-meshheading:19884907-Genotype,
pubmed-meshheading:19884907-Humans,
pubmed-meshheading:19884907-Imipramine,
pubmed-meshheading:19884907-Middle Aged,
pubmed-meshheading:19884907-Multivariate Analysis
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pubmed:year |
2010
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pubmed:articleTitle |
The CYP2C19*17 genotype is associated with lower imipramine plasma concentrations in a large group of depressed patients.
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pubmed:affiliation |
Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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