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Thread: Diazepam and Tagamet - how large is the potentiation?

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    Diazepam and Tagamet - how large is the potentiation? 
    #1
    It's well known that diazepam is potentiated by tagamet (cimetadine). I've reviewed the obvious search results, and while lots of people are talking about it being possible to potentiate diazepam, nobody seems to have said that they actually do so.

    Does anyone have any experience with how strong this potentiation is; ie, will diazepam potentiated by tagamet feel 10% stronger? 50%? 100%? Will it just last longer? How should I adjust a recreational dose to account for potentiation?

    Does anyone have a recommended dosing protocol with the cimetadine? (ie xxx mg this long before taking the diazepam, repeat every x hours)
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    #2
    300mg Cimetadine 15 minutes prior to 20mg diazepam.

    No appreciable difference from 20mg diazepam normally.
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    #3
    I normally take 400mg. cimetadine one hour before administration of x mg. of oral alprozolam. I've noticed no noticeable effects resulting from the cimetadine use, but I continue to do so for the placebo effect.
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    #4
    I do it. And GFJ. I feel as if it makes a difference, if only to prolong the duration of drug effects. Could be placebo, but there is in fact research on this (at least for alprazolam with GFJ). I'll look, post more if I can find experimental evidence...

    EDIT: For example (the first result in my google search), this study claims very strong support for the potentiation hypothesis:
    "Abstract
    "Grapefruit juice has been reported to markedly improve the bioavailability of triazolam, midazolam, terfenadine, cyclosporine and several dihydropyridine calcium channel blockers including felodipine, nifedipine, nitrendipine and nisoldipine. Because these drugs are metabolized by the hepatic cytochrome P450 isozyme (CYP) 3A4, the inhibitory effect of grapefruit juice is thought to results from inhibition of CYP3A4. In this study, our aim was to investigate the effects of grapefruit juice on plasma concentrations of diazepam. Eight healthy male and female subjects participated in this study. Oral (5 mg) diazepam was administered with either 250 ml water and grapefruit juice. Blood samples were collected for a 24 h period, and whole blood concentrations of diazepam were measured enzyme immunoassay. The mean AUC(0-24) of diazepam was increased 3.2-fold (P < 0.001) and Cmax was increased 1.5-fold (P < 0.05) by the grapefruit juice. Grapefruit juice postponed the tmax of diazepam from 1.50 h to 2.06 h (P < 0.01).
    * OZDEMIR et al. 1998. "Interaction between grapefruit juice and diazepam in humans"
    European journal of drug metabolism and pharmacokinetics 23 (1): 55-59.
    *http://cat.inist.fr/?aModele=afficheN&cpsidt=2240551
    These results seem suspiciously extreme, if I read them correctly. The AUC (area under curve) means something like total drugs in blood over that period, so tripling the dose seems absurd, unless it doubled the half-life or some such (I didn't do any math at all to guesstimate what that could result in for AUC); increasing the peak 1.5 times seems somewhat high, but not unreasonable; the last result, extending the TMax, means the peak was reached later with grapefruit juice, but that's not an especially important point since the peak was much higher anyway. Am I interpreting all those figures correctly -- anyone with chem/pharm/bio-med training?
    Last edited by socio; 31-12-2010 at 04:20.
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    #5
    Another study from the New England Journal of Medicine suggests Tagamet aka Cimetidine also has significant potentiation effects:
    "Clinical Importance of the Interaction of Diazepam and Cimetidine"
    David J. Greenblatt et al. 1984. N Engl J Med 310:1639-1643

    Abstract

    Cimetidine is known to impair the hepatic microsomal oxidation of diazepam, reducing its clearance and prolonging its half-life. We studied the clinical importance of this effect in 10 patients, who were receiving long-term treatment with diazepam for anxiety, tension, or difficulty in sleeping, in an eight-week double-blind controlled study during which the diazepam dosage remained constant. The study was in four two-week phases: base-line or adaptation, coadministration of cimetidine (300 mg) or matching placebo four times daily, crossover to the opposite treatment (placebo or cimetidine), and recovery treatment with diazepam alone.

    During the cimetidine phase, plasma concentrations of diazepam plus desmethyldiazepam rose an average of 57 per cent (P<0.005), then fell when cimetidine was withdrawn. However, there were no significant changes in scores on the digit-symbol-substitution test, a tracking task, or a reaction-time test. Clinical self-ratings indicated no increases in sedation, fatigue, or drowsiness. Patients experienced shortening of sleep latency (P<0.05) and an increase in self-rated depth or soundness of sleep (P<0.001) during the cimetidine period, but there were no changes in sleep duration or in the number of nocturnal awakenings.

    Although coadministration of cimetidine to diazepam-treated patients causes a large increase in plasma diazepam and desmethyldiazepam concentrations, the increase is of minimal clinical importance. --[url]http://www.nejm.org/doi/pdf/10.1056/NEJM198406213102505[\url]
    So, although it significantly raises plasma diazepam, there is few subjective or clinical changes. Weird. A similar study of methadone came to roughly the same conclusions (posted in a different thread).
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    cimetidine and omeprazole for diazepam 
    #6
    Bluelighter mygreenbic's Avatar
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    First off i notice a huge difference with cimetidine and diazepam. Also with omeprazole. After reading several threads on bl saying its placebo or just lengthened the effects, i was cynical and did some research. Here is what i found:

    Omeprazole May increase diazepam levels and enhance Effects
    Cimetidine, oral contraceptives, disulfiram May increase effects of diazepam with excessive sedation and impaired psychomotor function. effects.
    Here is the link:
    http://goo.gl/LemYc
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    #7
    Bluelighter toothpastedog's Avatar
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    This was when I was also using cimetidine to potentiate buprenorphine (which is pretty marked and very noticable). Dosing strategy I used with cimetidine and the benzos I list mirrors that I did with bupe: 200mg 30minutes prior to dose and 400mg minutes before dosing said benzo.

    With clonazepam, I have noticed no-little increase in either intensity of the drug's effects or duration (although possible increase in duration).

    With alprazolam I noticed marked increase in effects of the drug both in duration and intensity this short acting anxiolytic, although the intensity was markedly increase (primarily in a more euphoric and anti-anxiety way, not so much with increased sedation). W/o cimetidine, alprazolam tended to make me black out at the 1.5+mg range. W/ cimetidine, it never seemed to do so, although I found my ideal dose was 1.25-1.5mg anyways.

    With diazepam I notice little increase in the intensity of the drug, although duration seems marginally increased. Similar situation to clonazepam - not really a big difference with or without the cimetidine.

    This thread is of key importance here, and I find it very useful again and again: http://www.bluelight.ru/vb/threads/1...-CYP-450-Chart!
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    #8
    Bluelighter hangyourhead's Avatar
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    I noticed a lot of potentiation when taking Tagament ~30 mins prior to dosing my diazepam. Increase in sedation, euphoria (which is really subjective), muscle-relaxant properties enhanced, and duration of desired/therapeutic effects.
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