View Full Version : Pharmacology - Grapefruit Juice and Benzodiazepines
azrael2600
16-10-2006, 00:09
swim receved a new script for xanax and picked it up at the prescription at a local pharmacy. what suprised swim was the patient education paper that usually comes along with prescriptions. Swim was particularly interested in the part on how to use the medicine. Swim will quote the paper:
Eating grapefruit or drinking grapefruit juice while you are taking this medicine may increase the amount of this medicine in your blood, which may increase your risk for serious side effects.
swim was wondering what this was all about? how does grapefruit juice increase the amount of xanax in your blood?
could anybody clarify what this is about?
allyourbase
16-10-2006, 15:48
grapefruit juice is a mild cytosome inhibitor; theyre afraid SWIY might get high. and that could lead to dancing.
Forthesevenlakes
16-10-2006, 15:59
to SWIMs understanding, grapefruit juice would slow the metabolism of xanax, thus increasing the amount of xanax in the bloodstream, and the amount available to the brain.
This grapefruit juice phenomena works with many other drugs, too, SWIM's found it effective with potentiating DXM and opiates.
like ayb says...this combination could lead to dancing, so use caution and put on swiy's dancin' shoes.
azrael2600
17-10-2006, 01:48
swim tried an experiment this morning before taking swim's morning dose of xanax. swim drank an 8oz. glass of grapefruit juice on an empty stomach 30 min prior to taken swims morning dose. swim did notice a slight difference, in that swim felt slightly more buzzed, than if swim took swim's normal dose without without the grape fruit juice.
Wyborowa
01-11-2006, 03:27
Not i know that grapfruit potentiates xanax's effect, would it also work well with klonopin?
Siwm takes .5mg 4x's a day. If swim started drinkin grapefruit juice, would it increase the effects? Doesn't it have to be ocean spray only? thanks!
Riconoen {UGC}
01-11-2006, 05:16
I think it would since they are closely related. but I don't know.
Clonazepam (like alprazolam) is metabolised by the cytochrome P450 system of liver enzymes. Grapefruit juice is an inhibitor of these enzymes. Fewer enzymes = more clonazepam around.
Bear in mind that inhibiting P450 may well increase SWIY's risk of od: Proceed with caution.
SWIJ doesn't think the brand of juice will have much effect ;)
This trick only works with triazolobenzodiazepines (Xanax, Halcion) and Cimetidine inhibits the P450 enzyme subtypes that metabolize these drugs much more strongly than grapefruit juice. You get an increase in the AUC (area under the curve), Cmax, and drug clearance is also decreased. Try about 600 mg of generic tagamet about an hour before a xanax dose. Serzone is an even more potent inhibitor. Basically you can half your dose by predosing with cimetidine (w/ xanax or halcion).
calmascanbe
29-11-2006, 18:26
SWIM might be a little confused by the difference of oppinions about grapefruit juice doubling the potentcy of clonazepam. Would another SWIM be willing to clarify if it works or not with clonazepam? Thanks
Any experience is very welcome.
From rxlixt:
"Although clinical studies have not been performed, based on the involvement of the cytochrome P-450 3A family in clonazepam metabolism, inhibitors of this enzyme system, should be used cautiously in patients receiving clonazepam."
SWIJ has no direct experience to report however.
calmascanbe
30-11-2006, 19:15
Thanks for the reply Jatelka. SWIM personally has never tried the combination , but SWIM might in the near future.If SWIM does SWIM will update the results.
SWIdr has tried potentiating many benzos using different brands of grapefruit juice. This trick works on all the benzos SWIdr has tried it on (alprazolam, clonazepam, lorazepam, and diazepam). SWIY might want to be careful though, because different people metabolized their stomach contents different and one could OD or get basically the same results by using this trick.
smithdogg1
30-12-2006, 00:45
How much grapefruit juice does one have to drink in order to get noticeable effects? And should it be done 30 mins or so before taking the pill?
Well like SWIdr said, it depends on one's metabolisim to deduce the amount of grapefruit juice one would have to drink. SWIdr is roughly 200lbs and has a moderate (more on the slower side) metabolism and can drink up to 32 fl oz of pure grapefruit juice (most of the time less) to acheive the potentiate his benzos enough. Of course SWIY would (ballpark guess) probably have to drink around 8-16 fl oz, but decide for yourself. And yes, it works much better if SWIY drinks the juice from an hour to thirty minutes before he plans on ingesting the benzos.
There’s been quite a lot of conflicting information about whether or not various benzos are potentiated by grapefruit juice or not: So here for SWIY’s viewing pleasure is what SWIJ has been able to dig up.
Grapefruit juice inhibits Cytochrome P450 (CY3PA specifically), which is found both in the liver and the wall of the small intestine. These enzymes metabolise benzodiazepines. The theory is, is that if the enzymes are inhibited then there will be greater bioavailability of the drug (for example, requiring lower doses to get the same effect). However it’s not quite so simple. This effect only comes into play if the parent drug is subject to extensive first pass metabolism. Drugs with high oral bioavailability (because of low first pass metabolism) are not affected by enzyme inhibition significantly.
Obviously grapefruit juice does not have an effect if benzodiazepines are taken parenterally (IV or IM), because first pass metabolism is eliminated.
SWIJ has seen it stated in various places on the net that it is only ruby grapefruit that has effect: Not so. Most of the studies were done with normal white grapefruit.
So, here we go.
Benzos definitely potentiated by grapefruit juice:
Triazolam (Halcion), Diazepam (Valium) and Midazolam (Versed)
Benzos definitely NOT potentiated by grapefruit juice:
Alprazolam (Xanax)
Benzos theoretically potentiated by grapefruit juice, but effects probably not clinically significant (because of high oral bioavailability):
Clonazepam (Klonopin), Lorazepam (Ativan), Chlordiazepoxide, Flurazepam (Dalmane), Temazepam (Restoril)
NB: No studies have been done on these benzos specifically
Another factor that comes into play is the duration of intake of grapefruit juice. Triazolam particularly has been studied. Studies have shown that although a single glass of juice increases plasma concentrations and half-life, repeated glasses of juice over three days has an even greater effect. This effect lasts for about 3 days after discontinuation of grapefruit juice.
Some other tit bits gleaned: Grapefruit juice is not the only juice to inhibit CY3PA. Others having an effect are: black mulberry > wild grape > pomegranate > black raspberry. All however have less of an effect than grapefruit. Star Fruit also appears to be a potent enzyme inhibitor.
On a side note: Other downers affected by grapefruit juice are: Buspirone (strongly clinically significant), Zaleplon (moderate significance), and Zolpidem (unlikely to be clinically significant).
If any SWIY is interested SWIJ has uploaded a list of the abstracts to the archive. She has not been able to locate the full papers
Wyborowa
14-02-2007, 16:22
u guys are SURE grapefruit would help potentiate it?
1st of all Swim asked 2 phmarmcists and they said no reactions.
2nd, Xanax has agrapefruit warning on it...unlike Klonopin...
just my veiw, wat u guys think?
See this thread here...
http://www.drugs-forum.com/forum/showthread.php?t=26819
which SWIJ posted since this thread.
Wyborowa
14-02-2007, 18:00
oh, cmon! The PDR handbook even says u shouldn't eat or drink grapefruit juice!!! along with the label on the bottel script
The PDR has to be cautious. It has to list every possible adverse effect. There is a paper in the archive here...
http://www.drugs-forum.com/forum/local_links.php?action=jump&id=1321&catid=27
on the pharmacokinetics of Alprazolam with grapefruit juice. Whether SWIY agrees with the conclusions is up to them.
As SWIJ has said previously: She has no experience herself. If others do, then here might be a good place to post it.
Swia herself noticed a potentiation in effects with clonazepam when she was using them. she had read it increased the effect and got curious so tried it with a smaller amount then normal she had drunk the gf juice a hour before hand on an empty stomach before swia had 2 mg. She does not condone this but had noticed an increase in effects comparing to what would of been a small dose. DO not combine this mix with alcohol specially spirits, if u do the end result is not pretty..;)
u guys are SURE grapefruit would help potentiate it?
1st of all Swim asked 2 phmarmcists and they said no reactions.
2nd, Xanax has agrapefruit warning on it...unlike Klonopin...
just my veiw, wat u guys think?
Thats wierd most pharmacists know about the interactions between medications like the benzodiazepine family and grapefruit juice. Around SWIdr, most benzo prescriptions now contain a warning, along with the others like "This medication may cause dizziness", to not drink grapefruit juice while taking the medication.
SWIdr has tried the grapefruit potentiation on several benzos. In his experiences, grapefruit juice (ingested approx. 30 minutes before benzo) has a good potentiation effect on: Valium (Diazepam), Klonopin (Clonazepam), and Tranxene (Chlorazepate). Grapefruit juice seems to have a mild potentiation effect on: Xanax (Alprazolam), Ativan (Lorazepam), and Librium (Chlordiazepoxide).
csharpprogrammer
22-02-2007, 20:45
Does drinking grapefruit juice only work when taking benzos by mouth, or does it potentiate an IV dose too?
Does drinking grapefruit juice only work when taking benzos by mouth, or does it potentiate an IV dose too?
The answer is no. Grapefruit juice works by inhibiting liver enzymes, which can help potentiate a number of drugs. But when one IV's a drug, the first-pass metabolism in the liver is skipped, so grapefuit juice wouldn't help.
Just take and do all the things the warnings say not to,and SWIY will be styling,J/k.SWIM tested this with xanax and grapefruit juice,and would say got a 30% boost in effectiveness.Tagement tip sounds good.SWIM wouldn't mess around potentiating k-pin,they have a rediculus long half life as it is,SWIM is a benzoid ,and I cant take that build up after 2-3 months.If someone added to that build up,SWIY would probably lose basic motor control within a week.
pankreeas
25-03-2007, 12:48
unless you iv the grafefruit juice first
unless you iv the grafefruit juice first
Haha, this would be a new effective substrate to inject with:D ! "Don't worry, you're only going to feel feel a little pinch..." ;)
after reading this swim drank 2 glasses of g/f juice and swim tried 10m of valium and could tell a diff. to me it added to it
SWIM drank 500ml of grapefruit juice and then popped 20mg valium, the effects were clearly potentiated. SWIM felt as if he had popped 40mg valium, nice way to make his benzos last longer!
Any 1 kno if orange would juice up valium. Swim would tyr but im outta juice, and 25 miles from a store w/fresh juice
Not all citrus juices contain narningenin or DHB. For this reason, citrus juices such as orange juice have not been shown to affect this enzyme.2 (http://www.consumer-health.com/services/cons_take10.htm#2)
Different parts of the grapefruit also contain different amounts of these two substances. The peel of the grapefruit is thought to contain more than any other part of the fruit. It is uncertain if eating a grapefruit will cause the same effects as drinking grapefruit juice.
I just found this on the internet, so I think SWIrod is out of luck, only grapefruit seems to work.
thnks nargle saved swim a drive to the store
hoodabudda
26-04-2007, 07:53
does vitamin c play a role in this because all of these jucies sound like hi vitamin c juices.
[quote=Nargyle;252638]Not all citrus juices contain narningenin or DHB. For this reason, citrus juices such as orange juice have not been shown to affect this enzyme.
According to this it's not the vitamin c that does the trick, but actually the narningenin or dhb, so I think the vitamin c wouldn't affect at all the diazepam.
Swim has been trying a 1000mg of vitamin c w/other minerals its called emergeyc from/Wall----. Swim`s said it would cover benzo`s, along w/4 325mg of aspirn 2 hrs b4 urine test would work. It was as worthless as something called The Stuff which had a money back guarentee, which swim mailed back 3 months ago and is still waiting 4 refund, howerver with the emergencyC swim hasnt had a cold or sniffles once. thats about all it is good 4 it comes in a box of 36 pcks. it mixes w/4 ozs of water.
testodan
29-04-2007, 05:25
Does orange juice has an effect too?
^^^ No
Please read the rest of the posts in this thread!
hoodabudda
30-04-2007, 02:56
the antacid/antiulcer drug ranitidine (zantac if swim remebers correctly)has been proven to be a moderatly powerful inhibitor of the enzyme that removes both benzos and alcohol from the body which increases the effects noticably.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8494127&dopt=Abstract http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2044.1993.tb06944.x cimitadine(tagment) was used in these tests but ranitadine is listed as more effective than its cousin cimitadine at http://www.medscape.com/viewarticle/464898_4 many other drugs are in this family all with varying potencies.swim wonder if any of the variations would work better than ranitadine.
hoodabudda
30-04-2007, 03:00
^^^swim tried this with 1.25 mg lorazapam(ativan) and noticed a longer lasting high than usuall. he had absained from benzos(but not zolpidem/ambien IDK if there is cross tolerance.) for a week before so tolerance was minimal.swim wonders what a combo of this plus grape fruit juice would be like....mabey next week :)
Laudaphun
18-05-2007, 07:26
Temazepam (Restoril) definitely is potentiated by ruby red pink grapefruit juice in me... I really believe this to be true, but I am not so proud to admit there is a small chance that it could be placebo effect... I really am 95% sure that it potentiates temazepem.... speeking of which its time for bed.
hoodabudda
18-05-2007, 11:59
anyone else tried the acid reducer (zantac or pepsid or tagment)it really works quite well, the peak seems to last a lot longer probably by a good 20-30 min at least,swim reccomends it,it is now a must for swim he always has a few ranitadine incase he scores some benzos
allyourbase
18-05-2007, 14:25
SWIM has never found grapefruit juice to help benzodiazapines....it should in theory....but it hasnt in SWIM's practice.
SWIJ would like some more qualitative reports here:
How much benzo would it normally take to feel effect? How much grapefruit juice did the flamingo imbibe? How much benzo did it actually take to feel effect?
Experiences with the other juices mentioned are also most welcome
the little leprechaun that lives in swim's garden first drank 2 glasses of graperuit juice and 30 minutes later ingested 20mg valium, he says the feeling he got was similar to doing 40mg valium, he's really joyeus that now he can make his benzos last longer
, and the doctor won't get suspicious of him renewing his prescription too often
pankreeas
19-05-2007, 02:08
What about a tolerance re: needing more and more grapefruit juice? ask the leprechaun if he's ready to stock up on grapefruits! they aren't always in season you know. And in the offseason the juice can be more expensive effects wise than benzos.
the antacid/antiulcer drug ranitidine (zantac if swim remebers correctly)has been proven to be a moderatly powerful inhibitor of the enzyme that removes both benzos and alcohol from the body which increases the effects noticably.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8494127&dopt=Abstract http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2044.1993.tb06944.x cimitadine(tagment) was used in these tests but ranitadine is listed as more effective than its cousin cimitadine at http://www.medscape.com/viewarticle/464898_4 many other drugs are in this family all with varying potencies.swim wonder if any of the variations would work better than ranitadine.
Swim recently had to give a urine and swim had been on zantac for 1 year. The zantac didnt help a bit. Swim had been takin it easy on valium cause swim knew it was bout time for the urine. Swim had took zelnorm which is 4 irritable bowel syndrome, when swim took this 1 x a day swim had no trouble passing a urine, no matter how much valium swim used that month. The bad thing they took it off the market in the us. It was causin unsual bleeding and heart attacks. Last week swim was given somin in its place. In 3 weeks or so swim will let you knoif this covers it
allyourbase
19-05-2007, 13:50
SWIM has tried: 300 ml grapefruit juice 30 minutes prior to oral dosing with 4 mg alprazolam - no noticeable impact
600 ml grapefruit juice 1 hour after ingestion of 2 mg alprazolam - no noticable impact
6 ~ 27 oz glasses of (30% actual juice) ruby red grapefruit juice starting 45 minutes before and not finishing the juice until about half an hour after oral dosing with 2 mg clonazepam - no impact
swim has tried similar experiments with diazepam as well, to no avail. it would be nice if it worked as well as with opiates. so much money could be saved.
SWIM needs 2 mg of alprazolam to even feel it slightly. the clonazepam bit mentioned above occured during a "dry spell" and swim was left heavily dissappointed.
Laudaphun
22-05-2007, 05:01
to be a little more specific to a previous post, SWIM is prescribed 30mg restoril at bedtime. SWIM finds that if he takes his normal prescribed dose of 30mg more than 2 days in a row, that, on the third day there will be very little effect. SWIM discovered that he was able to extend this an extra day or two with the use of 4-8oz of ruby red grapefruit juice... basically just a couple mouthfuls to get the pills down. SWIM will admit that it is entirely possible that it could have been a placebo effect, however he's been regularly prescribed restoril for 1 1/2 years and was convinced enough on several occasions that, now he never takes his restoril without ruby red grapefruit juice (and on an empty stomach.)
SWIM is also prescribed librium, which he doesn't take very often and has never noticed any increase in effect with the same amount of the same juice.
TW_Agent
02-06-2007, 08:05
Hi everybody, :)
I'd like to find out if the grapefruit juice (as it impacts on the
cytochrome P450 enzymes or so) influences on the alprazolam (aka Xanax) half-time and its effect. I have read some texts about it, but there
is very poor information about just alprazolam. One source suggests even,
that this exactly drug does not interact with the juice. What is the
truth?
I ask because if it's so, then I could take less tablets of this cure to
get desired effect; I would like to save the tablets as it is not very
easy to get this cure - doctors but prescribe such ones so unwillingly,
although I personally have the anxiety problems.
I do not know if it depends on the dose and the juice quantity. Does
the casual carton grapefruit juice have the same P450-inhibiting
flavonoids content as the fresh fruit juice?
The most interesting doses for me are 0,5 or 0,75 mg of alprazolam and
about 100 ml of the juice.
I'd like to get possibly most precise info. I hope here are some
people who know about this case more than me - and they'll willingly
share their knowledge and experience... ;)
Or, if it doesn't work, maybe there are some other natural, and safe of
course, ways to prolong the alprazolam half-time and concentration in the
blood, and maybe you know about some of them?
Cheers to you!
http://www.medscape.com/medline/abstract/10907671
sorry folks, here is a cut and paste of the article previously linked ^^^...
"
Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam.
Psychopharmacology (Berl). 2000; 150(2):185-90 (http://www.medscape.com/medline/publicationbrowser/123?pmid=10907671) (ISSN: 0033-3158)
Yasui N; Kondo T; Furukori H; Kaneko S; Ohkubo T; Uno T; Osanai T; Sugawara K; Otani K
Department of Neuropsychiatry, Hirosaki University School of Medicine, Japan.
The effects of repeated ingestion of grapefruit juice, an inhibitor of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of both single and multiple oral doses of alprazolam, a substrate of CYP3A4, were examined. In study 1, eight healthy volunteers ingesting 600 ml/day water or grapefruit juice for 10 days took a single oral 0.8-mg dose of alprazolam on the eighth day. Plasma drug concentrations were monitored up to 48 h after alprazolam dosing together with evaluation of psychomotor function. Grapefruit juice altered neither the plasma concentrations of alprazolam at any time points, any pharmacokinetic parameters, nor the majority of psychomotor function parameters in subjects. In study 2, 11 patients with anxiety disorders receiving alprazolam (0.8-2.4 mg/day) ingested grapefruit juice (600 ml/day) for 7 days. Blood samples were collected before and during grapefruit juice ingestion and 1 week after its discontinuation together with an assessment of clinical status. Grapefruit juice altered neither the steady-state plasma concentration of alprazolam nor the clinical status in patients. The present study shows that grapefruit juice is unlikely to affect pharmacokinetics or pharmacodynamics of alprazolam due to its high bioavailability.
"
TW_Agent
15-06-2007, 16:56
OK, thanks. It's a pity.
And maybe some cures which inhibit the liver metabolism? I've recently found on the net that omeprazol - a stomach cure - inhibits that metabolism and can significantly prolong the P450-metabolised drugs' t1/2.
It'd be interesting, but it's the prescription drug.
Cheers :)
For those that are interested the full paper is in the archive here...
http://www.drugs-forum.com/forum/local_links.php?action=jump&id=1321&catid=27
TW_Agent
21-06-2007, 17:43
Aha... I see.
Big Fella
10-09-2007, 13:53
SWIM always welcome any placebo effect, because ultimatley it is the effect SWIY seeks, the exact manner in which that is achieved really doesn't matter.
Aside from the obvious dangerous of poly drug use, i.e benzo's + Alcohol, Benzo's + Opiate.
Does it matter if SWIY feels more potentation after watching 3 hours of Friends, it is all about the expeirence that is sought.
all_time_high
19-09-2007, 17:54
SWIM would like to know if grape juice can potentate nitrazepam. Any help would be appreciated
Wild grape juice is apparently a CY3PA inhibitor. Regular grape juice: No
SWIJ has to confess she has no idea what "Wild" grape juice is, she's certainly never come across it.
(Goes off to try and refind reference)
underglow18
30-09-2007, 01:38
will potentiation occur if a yellow bunny took the benzo sublingually?
merc11292
03-10-2007, 02:22
swim is a frequent user of diazapam for anxiety purposes and infrequently for recreation, swim doesnt completely understand how, but does know that grapefruit juice makes benzo's feel stronger, could anyone tell swim how grapefruit juice should be consumed with benzo's safely.
jimstern2588
08-10-2007, 07:15
I think the problem is that there are 2 types of klonopin... there is a tablet meant to be swallowed orally and there is also a tablet to be dissolved in mouth. So if what you have is the dissolving tablet, then I believe that the grapefruit juice would have no effect.
I think the problem is that there are 2 types of klonopin... there is a tablet meant to be swallowed orally and there is also a tablet to be dissolved in mouth. So if what you have is the dissolving tablet, then I believe that the grapefruit juice would have no effect.
See Jakelta's link a few posts up. Grapefruit juice is thought to shut down enzymes in your liver which normally destroy a specific type of benzo. With some benzos it has absolutely no effect pretty much, but with others it potentiates them. Unfortunately klonopin doesn't seem to be affected by grapefruit juice, regardless of the type of pill it comes as.
SWIM has used benzo's on and off in mild dosages for over 3 years. It is funny that Xanax is labeled with the grapefruit juice warning but Valium is not. I can't recall combining the two but I do love a pomegranate/cranberry combo and potentiation could be a small reason why ;)
Wild grape juice is apparently a CY3PA inhibitor. Regular grape juice: No
I'd like to have this one clarified, becuse I find conflicting info on this one. Could these 'white' and 'regular' be synonyms to 'red' and 'white' when talking about GFJ? Paracelsus claimed that both of these have activity. And according to his own experience white is even more effective, but from what I've gathered both of these work.
Bear in mind people that "Grape" and "Grapefruit" are 2 different things!
Grapes = Grow on vines, come in red, white and (apparently) "wild". Only "wild" grape juice is reported to have CY3PA activity (only reference I have been able to find is linked to above). The others are used to make wine.
Grapefruit = Citrus fruit, commonly eaten for breakfast. Both Ruby and White grapefruit juice have CY3PA activity
"Grape" does NOT = "Grapefruit"
Aaah, that clears things up. I got mixed up because in finnish grapefruit = greippi = grape pronounced in a finnish manner. For a grape there is a whole different, unrelated word.
Benzos theoretically potentiated by grapefruit juice, but effects probably not clinically significant (because of high oral bioavailability):
Clonazepam (Klonopin), Lorazepam (Ativan), Chlordiazepoxide, Flurazepam (Dalmane), Temazepam (Restoril)
Wouldn't it still make the effects last longer if the only metabolic pathway is through the inhibited hepatic cytochrome enzyme? And in that case it would prolong the effects of snorted benzodiazepines too, which are metabolised by this enzyme, right?
Paracelsus
05-12-2007, 17:03
trptamene (?) uploaded a trial with different amounts of grapefruit juice and midazolam (search it in the archive if you wish). It concluded that small (~200 ml) amounts of grapefruit juice inhibit only intestinal CYP3A (and therefore just raise bioavailability due to elimination of first-pass metabolism), but large amounts (can't remember the exact amounts) were shown to also inhibit hepatic (liver) CYP3A.
The obvious conclusion is that large amounts of grapefruit juice can, besides potentiating CYP3A substrates by inhibiting first-pass metabolism, also prolong their duration. This most likely also applies to injected/snorted benzodiazepines. Although this is, to my knowledge, the only study about how large amounts of grapefruit juice work, the implications are certainly interesting.
I'm feeling magnanimous (and I love to get people looking at the archive!) so here are some links for those who can't be bothered to search...
http://www.drugs-forum.com/forum/local_links.php?action=jump&id=3438&catid=129
http://www.drugs-forum.com/forum/local_links.php?action=jump&id=1321&catid=129
be warned: I'm not always this generous :p
Thanks for the links. I could've researched but I was under the impression it's the hepatic enzyme GFJ has effect on. In fact, I thought the liver is the only place where cytochrome enzymes live.
Talking of links, I've managed to find the full articles on the effects of other fruit juices on cytochrome.
Theoretically: pomegranate, star fruit, black mulberry and (the previously mentioned) "wild grape" are also effective inhibitors
have also found a fascinating article on the different effects of different compnonents of GFJ on different cytochrome enzymes
Acrobat seems to be screwed currently, so the archive links will have to wait: So watch this space....
Laudaphun
05-01-2008, 02:52
Potent CYP3A Inhibitors
Azole antifungal agents— Ketoconazole and itraconazole are potent CYP3A inhibitors and have been shown in vivo to increase plasma alprazolam concentrations 3.98 fold and 2.70 fold, respectively. The coadministration of alprazolam with these agents is not recommended.
Other azole-type antifungal agents should also be considered potent CYP3A inhibitors and the coadministration of alprazolam with them is not recommended (see
CONTRAINDICATIONS).
Drugs demonstrated to be CYP 3A inhibitors on the basis of clinical studies involving alprazolam (caution and consideration of appropriate alprazolam dose reduction are recommended during coadministration with the following drugs)
Nefazodone—Coadministration of nefazodone increased alprazolam concentration two-fold.
Fluvoxamine—Coadministration of fluvoxamine approximately doubled the maximum plasma concentration of alprazolam, decreased clearance by 49%, increased half-life by 71%, and decreased measured psychomotor performance.
Cimetidine—Coadministration of cimetidine increased the maximum plasma concentration of alprazolam by 86%, decreased clearance by 42%, and increased half-life by 16%.
The above was copy 'n pasted from a xanax package insert. While this isn't exactly grapefruit juice, it basically still working in a similar manner if I am correct. SWIM will have to do an experiment on his lab rat... 86% should be enough to definitely notice or not.
A new entry has been added to Drugs Archive by chrisn
Description:
Clinical Pharmacology and Therapeutics Vol 58 1
Kuperschmidt et al
Pretreatment with grapefruit juice is associated with increased bioavailability and changes in the pharmacodynamics of midazolam that may be clinically important, particularly in patients with other causes for increased midazolam bioavailability such as advanced age, cirrhosis of the liver, and administration of other inhibitors of cytochrome P450.
To check it out, rate it or add comments, visit Interaction between grapefruit juice and midazolam in humans (1995) (http://www.drugs-forum.com/forum/local_links.php?linkid=4829&catid=129)
The comments you make there will appear in the posts below.
A new entry has been added to Drugs Archive by chrisn
Description:
Clinical Pharmacology and Therapeutics, August 1995
Hukkinen et al
Grapefruit juice can increase the plasma concentrations and effects of oral triazolam.
To check it out, rate it or add comments, visit Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice (1995) (http://www.drugs-forum.com/forum/local_links.php?linkid=4830&catid=129)
The comments you make there will appear in the posts below.
crunchyblack
12-04-2008, 23:00
This is not too surprising as we all know grapefruit juice does the same thing for opiates.
Kizzzles
22-10-2008, 06:32
I do know that it does have an effect on Xanax. I drank some white grape fruit juice and I couldnt hardly wake up the next day, had like 2 redbulls just to get thru the day. I was so ready to go back to sleep. The whole weekend just floated by.... Havent used it on valium...
Laudaphun
22-10-2008, 10:01
Genetics is unraveling many new and interesting things... we are learning the genes responsible for production of specific protiens and much more! Different benzos are broken down by different CYP's SWIM doesn't have her chart in front of her at the moment, but the inhibitor in grapefruit juice is very specific, CYP3A4 I believe, which accounts for a large portion of pharmaceuticals, but it is not solely responsible for metabolism of all benzos.
Plus, you have to take into account that benzos such as diazepam, chlordiazpoxide, and some of the other older benzos can have MANY active metabolites which have VERY long half-lifes and exhibit a large amount of their effect by build-up in the body in regular users. Newer benzos, such as clonazepam, alprazolam, and others do not have active metabolites and as such do not build up in the body like some of the others. Even though all of these drugs "feel" similar and are in the same class, a very minor alteration to a chemical structure can have drastic effects on the manner in which it interacts with the body. Plus, with genetics, and mutations that can occur, one person could experience a significant increase in effect from GFJ while another with the same tolerance may not. The gene responsible for CYP3A4 is very ... SWIM forgets the word... polymorphic, meaning it can cause cause it to be expressed a great deal more or less than normal... She is fuzzy on this and will have to refresh myself on the special characteristics of CYP3A4 that make it so interesting!
Plus, remember the big issue with insurance in the medical field and fear of lawsuits... they slap warning stickers if there is even a slight chance of interaction.
kaczynski
22-10-2008, 22:45
grapefruit juice is a mild cytosome inhibitor; theyre afraid SWIY might get high. and that could lead to dancing.
haha awesome:vibes:
yosmokinman
16-11-2008, 01:03
Well, swim just tried this. Drank abot 24ml Gf juce +/- 45 min. ago followed by 210mg oxazepam and I must say I am noticing a nice buzz, as if I hade taken more, works for swim aparently :) I'ts not hugly intence, but more than without ;)
Swim got a tollorance so you might want to lower your dose.
No persona experience wit kpins or zannys mix with GFJ, plenty woithout though,,, so IDK???
claroscura
17-11-2008, 07:02
...Or one might skip the grapefruit juice and the IV and simply take that sucker sublingually. I don't know about Xanax specifically, but most benzos are prescribed for issues like anxiety, and it is possible to dissolve them under the tongue, where they are quickly absorbed into the blood stream through the mucous membrane. The onset is faster, making this a recommended method for anyone experiencing a panic attack, or for, say, someone who just wants to get a little higher (or lower, as the case may be) a little faster.
But if one is fond of grapefruit juice, then hell, why not?
Laudaphun
18-11-2008, 14:39
The only problem SWIM sees with GFJ is that the particular enzymes that it inhibits, are responsible for a host of other metabolisms... So, if one is using other substances it is well to take this into consideration as well. SWIM will get back to this later and edit this post, but there was a table she was creating listing the specific enzymes responsible for metabolism of different substances, along with substances that inhibit or induce metabolism.