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

[drug-bot]

[top]Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone.

Benmebarek M, Devaud C, Gex-Fabry M, Powell Golay K, Brogli C, Baumann P, Gravier B, Eap CB.
Service of Medicine and Penitentiary Psychiatry, University Department of Adult Psychiatry, Lausanne, Switzerland.
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.
PMID: 15229464 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/15229464
swim decided to put this in this section rather than the opiate one cause it deals more with pharmacology, if mods disagree please move it.
swim searched the document archives here on the forum regarding methadone and couldnt find it, if he overlooked it swim apologizes and feel free to delete.

for the last 2 days swim experimented by drinking a large glass of grapefruit juice about an hour before gettin his 90mg of methadone and another glass after he got home (about 15min). he didnt experience any euphoria but definetly noticed a slightly more sedated state of being, as well as a slight increase in the 'i dont give a fuck' attitude opiate provide him, but all in all, like the report states theres only a 'modest increase in methadone bioavailability', so there was nothing sensational about it other than what was mentioned by swim earlier in this paragraph (which wasnt really sensational ).

tommorrow swim will drink some juice about 6hrs prior to as well as 1hr prior to doseing on methadone as well as 15min after to see if the build up of the juices enzyme CYP3A in his liver produces a stronger efffect/intoxication, he'll report on findings tommorow.