Linked Life Data

16236141

Source:http://linkedlifedata.com/resource/pubmed/id/16236141

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-10-20
pubmed:abstractText
The antidepressant fluoxetine is administered as racemic mixture of two enantiomers (S- and R-fluoxetine). While S- and R-fluoxetine are equipotent in blocking serotonin reuptake, the enantiomers of the demethylated metabolite, norfluoxetine, show marked differences in pharmacological activity, S-norfluoxetine being about 20 times as potent as R- norfluoxetine as a serotonin reuptake inhibitor. In vitro and in vivo data suggest that the metabolism of fluoxetine to norfluoxetine is stereoselective and mediated, at least in part, by the polymorphic cytochrome P450 (CYP) isoenzymes CYP2D6, CYP2C9 and CYP2C19. In the present study, the influence of CYP2D6, CYP2C9 and CYP2C19 polymorphisms on the steady-state plasma concentrations of fluoxetine and norfluoxetine enantiomers was evaluated in 78 patients receiving chronic fluoxetine treatment (10-60 mg/day). The plasma concentrations of fluoxetine and norfluoxetine enantiomers were measured and CYP2D6, CYP2C9 and CYP2C19 genotypes were analyzed. No statistically significant relationship was identified between CYP2D6 or CYP2C19 genotypes and the dose normalised plasma concentrations of any of the enantiomers or the active moiety (i.e. the sum of S-fluoxetine, R-fluoxetine and S-norfluoxetine). However, the plasma concentration of S-norfluoxetine was very low in the only CYP2D6 poor metaboliser. Furthermore, the median S-norfluoxetine/S-fluoxetine ratios were higher in homozygous than in heterozygous extensive metabolisers (P<0.05). Among homozygous extensive metabolizers for CYP2D6, patients homozygous for CYP2C9*1 had lower dose-normalized R-fluoxetine concentrations and lower active moiety levels compared with those carrying detrimental CYP2C9 alleles (P<0.05). These results suggest that CYP2D6 and CYP2C9 polymorphisms contribute to the interindividual variability in fluoxetine pharmacokinetics at steady-state.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1742-7835
pubmed:author
pubmed:issnType
Print
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
296-301
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16236141-Adolescent, pubmed-meshheading:16236141-Adult, pubmed-meshheading:16236141-Aged, pubmed-meshheading:16236141-Alleles, pubmed-meshheading:16236141-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:16236141-Chromatography, High Pressure Liquid, pubmed-meshheading:16236141-Cytochrome P-450 CYP2D6, pubmed-meshheading:16236141-DNA, pubmed-meshheading:16236141-Female, pubmed-meshheading:16236141-Fluoxetine, pubmed-meshheading:16236141-Genotype, pubmed-meshheading:16236141-Humans, pubmed-meshheading:16236141-Male, pubmed-meshheading:16236141-Middle Aged, pubmed-meshheading:16236141-Mixed Function Oxygenases, pubmed-meshheading:16236141-Polymorphism, Genetic, pubmed-meshheading:16236141-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16236141-Serotonin Uptake Inhibitors, pubmed-meshheading:16236141-Stereoisomerism
pubmed:year
2005
pubmed:articleTitle
Influence of CYP2C9, 2C19 and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine.
pubmed:affiliation
Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy. gabriella.scordo@medsci.uu.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't