Titre
Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Benmebarek, M.
Auteure/Auteur
Devaud, C.
Auteure/Auteur
Gex-Fabry, M.
Auteure/Auteur
Powell Golay, K.
Auteure/Auteur
Brogli, C.
Auteure/Auteur
Baumann, P.
Auteure/Auteur
Gravier, B.
Auteure/Auteur
Eap, C.B.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0009-9236
Statut éditorial
Publié
Date de publication
2004
Volume
76
Numéro
1
Première page
55
Dernière page/numéro d’article
63
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
BACKGROUND AND OBJECTIVES: Cytochrome P450 (CYP) 3A4 is the main CYP isozyme involved in methadone metabolism. We investigated the influence of grapefruit juice, which contains inhibitors of intestinal CYP3A, on the steady-state pharmacokinetics of methadone. METHODS: For 5 days, 8 patients undergoing methadone maintenance treatment received 200 mL water or grapefruit juice 30 minutes before and again together with their daily dose of methadone. Blood sampling for R-, S-, and R,S-methadone plasma determination was performed over a 24-hour period. CYP3A activity was determined by measuring the plasma 1'-hydroxymidazolam/midazolam ratio. RESULTS: A decrease in the midazolam ratio was measured in all patients after grapefruit juice (mean +/- SD before grapefruit juice, 9.3 +/- 5.9; mean +/- SD after grapefruit juice, 3.9 +/- 1.2; P <.05). Grapefruit juice led to a mean 17% increase in the area under the curve extrapolated to 24 hours for both enantiomers of methadone (range, 3% to 29% [P <.005]; range, -4% to 37% [P <.05]; and range, 1% to 32% [P <.01]; for R-, S-, and R,S-methadone, respectively). A similar increase in peak level and decrease in apparent clearance were measured with grapefruit juice, whereas time to peak level, terminal half-life, and apparent volume during the terminal phase of R-, S-, and R,S-methadone were not affected by grapefruit juice. No symptom of overmedication was either detected by the clinical staff or reported by the patients. CONCLUSIONS: Grapefruit juice administration is associated with a modest increase in methadone bioavailability, which is not expected to endanger patients. However, it cannot be excluded that a much stronger effect may occur in some patients, and thus grapefruit juice intake is not recommended during methadone maintenance treatment, in particular in patients initiating such a treatment.
PID Serval
serval:BIB_19CBC2A79031
PMID
Date de création
2008-03-10T09:53:56.637Z
Date de création dans IRIS
2025-05-20T18:16:27Z