Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone

Details

Serval ID
serval:BIB_19CBC2A79031
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone
Journal
Clinical pharmacology and therapeutics
Author(s)
Benmebarek M., Devaud C., Gex-Fabry M., Powell Golay K., Brogli C., Baumann P., Gravier B., Eap C.B.
ISSN
0009-9236
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
76
Number
1
Pages
55-63
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
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.
Keywords
Adult, Area Under Curve, Beverages, Citrus paradisi, Cytochrome P-450 Enzyme System, Female, Humans, Male, Metabolic Clearance Rate, Methadone, Middle Aged, Stereoisomerism
Pubmed
Web of science
Create date
10/03/2008 10:53
Last modification date
20/08/2019 12:50
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