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Thread: Grapefruit Juice Enhances the Exposure to Oral Oxycodone

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    Grapefruit Juice Enhances the Exposure to Oral Oxycodone 
    #1
    I know this isn't normally the kind of thing we post in BDD, but I found the results of this study so amazing I figured it was worth sharing. I posted it as a reply in another thread, but I really feel this information shouldn't be overlooked. They are talking about 1.5 fold increases in peak plasma concentration and 1.2 fold increase in half life (with a very low p-value for those who like their statistics significant). The test subjects ingested 200ml of grapefruit juice 3 times per day for 4 days before the oxycodone was administered. I think this is evidence enough to state that drinking grapefruit juice on a daily basis can have a very significant impact on oxycodone metabolism.

    Grapefruit juice enhances the exposure to oral oxycodone
    Nieminen T.H., Hagelberg N.M., Saari T.I., Neuvonen M., Neuvonen P.J., Laine K. and Olkkola K.T.
    Basic and Clinical Pharmacology and Toxicology 2010 107:4 (782-788)
    Grapefruit juice alters the concentrations of many CYP3A substrates. The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration-time curve (AUC0-∞) by 1.7-fold (p < 0.001), the peak plasma concentration by 1.5-fold (p < 0.001) and the half-life of oxycodone by 1.2-fold (p < 0.001) as compared to the water. The metabolite-to-parent AUC0-∞ ratios (AUCmAUC p) of noroxycodone and noroxymorphone decreased by 44% (p < 0.001) and 45% (p < 0.001), respectively. Oxymorphone AUC0-∞ increased by 1.6-fold (p < 0.01) after grapefruit juice, but the AUC mAUCp remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use.
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    #2
    Bluelighter ro0ga's Avatar
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    Not quite. If you read closely, while it says that "grapefruit products may increase the concentration and effects of oxycodone in clinical use", it also states that "pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice". The wording is a bit dodgy, and while it's true that it may alter the concentrations of certain metabolites of oxycodone, the overall outward effects on the body are "modest".

    It says that pharmacokinetics (what the body does to the drug) changed somewhat significantly, pharmacodynamics (what the drug does to the body) changed only modestly. Pharmacodynamics are chiefly responsible for the effect of the drug.

    I'm not saying grapefruit juice doesn't have the potential to potentiate the effects of certain drugs, only that in this particular study, it doesn't exactly give way to an astounding conclusion that grapefruit juice will significantly alter the effects of oxycodone. From my experience both personally and from pharmacology courses in pharmacy school, is that you need much more than 200 ml to have appreciable effects in terms of analgesia and euphoria with oxycodone.
    Last edited by ro0ga; 21-04-2012 at 00:02.
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    #3
    Addendum: Another study showing the impact of grapefruit juice on loperamide. This seems to bear out the assertion that grapefruit juice can significantly impair CYP3A activity resulting in altered pharmacokinetics. It is worst pointing out however that even in the oxycodone study, pharmacodynamic changes were subjective only, which means your mileage may vary.

    Grapefruit juice increases systemic exposure of loperamide without consequent central nervous system opiate-like effects in healthy volunteers
    Wolf K.K., Li Y., Connolly E.A., Won C.S., Scarlett Y.V. and Paine M.F.
    Clinical Pharmacology and Therapeutics 2011 89 SUPPL. 1 (S7)
    Background: Loperamide (LOP), a dual CYP3A/P-gp substrate and anti-diarrheal agent, is a potent mu opioid receptor agonist that lacks central nervous system (CNS) opiate-like effects. Anecdotal reports suggested consumption with grapefruit juice (GFJ) could enhance systemic LOP exposure to an extent sufficient to produce CNS effects. Accordingly, effects of GFJ on LOP pharmacokinetics (PK) and pharmacodynamics (PD) were evaluated in healthy volunteers. methods: By randomized crossover design, subjects (n = 16) received LOP (16 mg) with 240 mL GFJ or water; greater than two weeks separated each phase. Blood and dark-adapted pupil diameter, the most sensitive measure of CNS opiate-like effect, were obtained over 72 h. Morphine (0.07 mg/kg) served as a positive control for PD effect. Plasma LOP and N-desmethylloperamide (dLOP) concentrations were measured by LC/MS/MS. LOP PK and PD outcomes were determined by non-compartmental methods. results: GFJ altered LOP PK but not LOP PD or dLOP PK (see table). Morphine decreased geometric mean pupil diameter, relative to baseline, by 2.1 mm (p<0.001). conclusion: The increase in systemic LOP exposure with no change in terminal t1/2 with GFJ is consistent with inhibition of intestinal CYP3A/P-gp by GFJ. The lack of effect on dLOP PK suggests multiple processes contribute to dLOP disposition. The lack of consequent effect on pupil diameter indicates GFJ has no CNS liability with LOP. Supported by NIH (UL1RR025747 and GM077482).(Table Presented).
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    #4
    Bluelight Crew effie's Avatar
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    I'll leave this here for now, but maybe tomorrow I'll move it to Other Drugs, as they have a potentiation megathread and this would be perfect there - the thread is in the OD Directory

    Not got time to read that properly now, sorry, but thank you for posting. Do you have a link to the source?
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    #5
    Quote Originally Posted by ro0ga View Post
    Not quite. If you read closely, while it says that "grapefruit products may increase the concentration and effects of oxycodone in clinical use", it also states that "pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice". The wording is a bit dodgy, and while it's true that it may alter the concentrations of certain metabolites of oxycodone, the overall effects on the body are "modest".

    It says that pharmacokinetics (what the body does to the drug) changed somewhat significantly, pharmacodynamics (what the drug does to the body) changed only modestly. Pharmacodynamics are chiefly responsible for the effect of the drug.
    Yes, I am aware, and posted as much in my addendum, which I posted before reading your reply. The fact remains, there is evidence to show grapefruit juice increases plasma levels of oxycodone, as well as half life. Considering grapefruit juice is cheap, legal and readily available, there is enough evidence here, in my opinion, to support the consumption of grapefruit juice.
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    #6
    Quote Originally Posted by effie View Post
    I'll leave this here for now, but maybe tomorrow I'll move it to Other Drugs, as they have a potentiation megathread and this would be perfect there - the thread is in the OD Directory

    Not got time to read that properly now, sorry, but thank you for posting. Do you have a link to the source?
    Yes and no. The source for the first article is Basic and Clinical Pharmacology and Toxicology 2010 107:4 (782-78. The article itself I was able to access via my universities online access to archives, and was found via http://www.embase.com/. You would need a login and password to access the actual article. I have only presented the abstract here, as the article itself is copyright, and I am sure posting copyright material is against the Bluelight terms.
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    #7
    Bluelighter ro0ga's Avatar
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    Quote Originally Posted by SPC123 View Post
    Yes, I am aware, and posted as much in my addendum, which I posted before reading your reply. The fact remains, there is evidence to show grapefruit juice increases plasma levels of oxycodone, as well as half life. Considering grapefruit juice is cheap, legal and readily available, there is enough evidence here, in my opinion, to support the consumption of grapefruit juice.
    I agree...it will increase plasma levels of oxycodone and it's "better" metabolites, but it's overall outward effect, at least with the volume of grapefruit juice analyzed, is minimal. And not to seem disagreeable, but your addendum focuses on loperamide and not oxycodone. The principle is the same, but you're talking about two different drugs, which is like comparing apples and oranges. The whole CYP3A4 inhibition is the same, but just because it has significant effects on one drug doesn't mean doesn't mean it works that way across the board.

    But overall you're right, grapefruit juice is cheap, legal, and available...so if you're looking to increase your buzz, it can't hurt. Just don't go into with huge expectations. I think if you're going to try and go this route, it's better to get some OTC cimetidine.

    And yes, there is certainly overwhelming evidence to support the consumption of grapefruit juice...it tastes pretty good IMO.
    Last edited by ro0ga; 21-04-2012 at 00:21.
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    #8
    I have personally tried drinking grapefruit juice prior to consuming oxycodone and found minimal results. BUT, I have not tried regular consumption of grapefruit juice over a period of days. One could easily increase the amount of grapefruit juice to even 500ml 3x daily for 4-5 days prior to consuming oxycodone. As well the study only used 10mg of oxycodone, which is a fairly low dose even for someone who is opiate naive. There is certainly no guarantee that this will increase your buzz, but increasing the amount of grapefruit juice consumed, plus increasing the amount of oxycodone taken (I would take 60-80mg) could very well have a noticeable impact.

    My point isn't to say "drink grapefruit juice, double your buzz!" It's simply to show the evidence supports the theory that grapefruit juice impedes CYP3A which leads to increased peak plasma levels and longer half life. Considering the cost, legality and availability of grapefruit juice (and as you said, it tastes pretty good too!) it makes sense to at least try this combination. Some might find a real impact!
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    #9
    Greenlighter
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    very well said, thank you both
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    #10
    Bluelighter ParappaTheRapper's Avatar
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    not to mention that WGJ is delicious, though an acquired taste..
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    #11
    Bluelighter Pilll_head's Avatar
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    The problem with grapefruit juice is that it delays gastric emptying which will delay absorption of oxy = lesser buzz. I switched to Tagamet (600 mg) a couple of years ago which is a moderately strong CYP inhibitor. GFJ just tastes so nasty also.
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