Cytochrome P450 2D6 genotype and methadone steady-state concentrations

Détails

ID Serval
serval:BIB_7A0AF50871FA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cytochrome P450 2D6 genotype and methadone steady-state concentrations
Périodique
Journal of clinical psychopharmacology
Auteur(s)
Eap C.B., Broly F., Mino A., Hämmig R., Déglon J.J., Uehlinger C., Meili D., Chevalley A.F., Bertschy G., Zullino D., Kosel M., Preisig M., Baumann P.
ISSN
0271-0749
Statut éditorial
Publié
Date de publication
2001
Peer-reviewed
Oui
Volume
21
Numéro
2
Pages
229-234
Langue
anglais
Notes
Publication types: Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
A genetic polymorphism of cytochrome P450 2D6 has been described with the existence of poor (zero functional genes), extensive (one or two functional genes), and ultrarapid metabolizers (three or more functional genes). The authors measured the steady-state trough (R)- (i.e., the active enantiomer), (S)-, and (R,S)-methadone plasma levels in opiate-dependent patients receiving methadone maintenance treatment (MMT) and genotyped them for cytochrome P4502D6. The patients' medical records were reviewed to assess the outcome of the MMT with regard to the absence of illicit opiate consumption and to the absence of withdrawal complaints in ultrarapid and poor metabolizers. Of 256 patients included, 18 were found to be poor metabolizers, 228 to be extensive metabolizers, and 10 to be ultrarapid metabolizers. Significant differences were found between genotypes for (R)- (p = 0.024), (S)- (p = 0.033), and (R,S)-methadone (p = 0.026) concentrations to dose-to-weight ratios. For (R)-methadone, a significant difference was found between ultrarapid metabolizers and poor metabolizers (p = 0.009), with the median value in the former group being only 54% of the median value in the latter group. These results confirm the involvement of cytochrome P450 2D6 in methadone metabolism. Although the difference was nonsignificant (p = 0.103), 13 (72%) of the 18 poor metabolizers and only 4 (40%) of the 10 ultrarapid metabolizers were considered successful in their treatment. More studies are needed to examine the influence of the ultrarapid metabolizer status on the outcome of the MMT.
Mots-clé
Adolescent, Adult, Analysis of Variance, Confidence Intervals, Cytochrome P-450 CYP2D6, Female, Genotype, Humans, Male, Methadone, Middle Aged, Narcotics, Opioid-Related Disorders, Polymorphism, Genetic, Statistics, Nonparametric
Pubmed
Web of science
Création de la notice
10/03/2008 11:38
Dernière modification de la notice
03/03/2018 18:33
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