Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses.

Détails

ID Serval
serval:BIB_50BEAD87FFE3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses.
Périodique
Drug and alcohol dependence
Auteur(s)
Shinderman M., Maxwell S., Brawand-Amey M., Golay K.P., Baumann P., Eap C.B.
ISSN
0376-8716
Statut éditorial
Publié
Date de publication
2003
Peer-reviewed
Oui
Volume
69
Numéro
2
Pages
205-11
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
We examined in vivo the influence of cytochrome P4503A4 (CYP3A4) activity, measured by the 30 min plasma 1'OH-midazolam/midazolam ratio after oral administration of 7.5 mg midazolam, on the methadone steady-state trough plasma concentrations in a group of 32 patients in methadone maintenance treatment. Patients were grouped as receiving 'low' (up to 99 mg/day, n = 10), 'high' (100-199 mg/day, n = 11) and 'very high' (> or = 200 mg/day, n = 11) doses of methadone, and the CYP3A4 metabolic activity was compared between the three groups. (S)-methadone and (R,S)-methadone, but not (R)-methadone, concentrations to dose ratios significantly correlated with the midazolam ratios (r(2) = -0.17, P = 0.018; r(2) = -0.14, P = 0.032; r(2) = -0.10, P = 0.083, respectively), with a 76% higher CYP3A4 activity in the very high-dose group as compared with the low-dose group. Significant differences in the CYP3A4 activity were calculated between the three groups (P = 0.0036), and group-to-group comparisons, using the Bonferroni correction, showed a significant difference between the low-dose and the very high-dose group (P = 0.0039), between the high-dose and the very high-dose group (P = 0.0064), but not between the low-dose and the high-dose group (P = 0.070). The higher CYP3A4 activity measured in patients receiving very high methadone doses could contribute to the need for higher doses in some patients, due to an increased metabolic clearance. This, however, must be confirmed by a prospective study.
Mots-clé
Adult, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme System, Dose-Response Relationship, Drug, Female, Humans, Male, Methadone, Middle Aged, Narcotics, Opioid-Related Disorders, Stereoisomerism
Pubmed
Web of science
Création de la notice
10/03/2008 11:53
Dernière modification de la notice
03/03/2018 17:09
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