Historique
Périodique
Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses
(Activité métabolique du cytochrome P4503A4, concentrations sanguines en méthadone et doses de méthadone)
Auteur(s) :
SHINDERMAN, M. ;
MAXWELL, S. ;
BRAWAND-AMEY M. ;
GOLAY, K. P. ;
BAUMANN, P. ;
EAP C. B.
Année
2003
Page(s) :
205-211
Langue(s) :
Anglais
Refs biblio. :
36
Domaine :
Drogues illicites / Illicit drugs
Discipline :
PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods)
Note générale :
Drug and Alcohol Dependence, 2003, 69, (2), 205-211
Note de contenu :
fig. ; tabl.
Résumé :
ENGLISH :
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' (> = 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 (r2 = -0.17, P = 0.018; r2 = -0.14, P = 0.032; r2 = -0.10, P = 0.083, respectively), with a 76`%o 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. (Review's abstract.)
Affiliation :
Unit Biochem. Clin. Psychopharmacol., Univ. Dept. Adult Psychiatr., Hôp. Cery, rte de Cery, CH 1008 Prilly-Lausanne
Suisse. Switzerland.
Suisse. Switzerland.