• BASIC DRUG
    DISCUSSION
    Welcome to Bluelight!
    Posting Rules Bluelight Rules
    Benzo Chart Opioids Chart
    Drug Terms Need Help??
    Drugs 101 Brain & Addiction
    Tired of your habit? Struggling to cope?
    Want to regain control or get sober?
    Visit our Recovery Support Forums
  • BDD Moderators: Keif’ Richards | negrogesic

Hydroxyzine and oxycodone metabolism/potentiation

Status
Not open for further replies.
Well cimetidine will certainly increase bioavailability and half-life significantly but unfortunately you'll have to sacrifice some potency.

Give it a go, you're the only one who can evaluate its benefit to you. I would suggest you do the same with hydroxyzine because as I mentioned before its inhibition of liver enzymes is mild, it has its own analgesic mechanism, and could add to the sedation of oxycodone therefore increasing relaxation.

Chrome, this forum is not about telling people they are wrong, so next time when you want to think only about yourself, remember this isn't your thread

I'm not even sure how to respond to that. When someone called you out on amphetamine and MDMA serotonin syndrome, I provided the study to back your statement up. My aim is not not to prove you wrong, but to state the facts. This is why it's called drug discussion, not LaCsters experiences.

Here is someone else that agrees and is objective:

There is a common misconception among opioid users in this forum, other forums, & on the street, and that is: a good potentiator for opiates or opioids is cimitidine (more commonly known as tagamet).

The theory is that because cimitidine inhibits the CYP3A4 liver enzyme which is responsible for breaking down many opiates/oids into inactive metabolites (noroxycodone, norhydrocodone, etc..) that the opiate/opioid in question will have an increased effect & longer duration. While this is true to a certain extent, there is a vital peice of information regarding the pharmokinetics of cimitidine & it's enzyme inhibition that is widely overlooked by the opiaficionados out there.

See not only does cimitidine inihibit the CYP3A4 enzyme it is also an inhibitor of a wide range of isozymes of the P450 enzyme system. In addition to the CYP3A4 enzyme, cimitidine (tagamet) also inhibits CYP1A2, CYP2C9, CYP2C19, CYP2E1, & most importantly the CYP2D6 liver enzyme.

The opiates/opioids codeine, hydrocodone, & oxycodone are all CYP2D6 substrates meaning they all involve metabolism by the enzyme CYP2D6 on some level. Specifically codeine as many, if not all, of us well know metabolizes into morphine via CYP2D6, hydrocodone is metabolized into hydromorphone via CYP2D6, & oxycodone is metabolized into oxymorphone via CYP2D6.

These metabolites I have just mentioned are all much stronger than codeine, oxycodone, & hydrocodone alone thus they are NOT good candidates for cimitidine (tagamet) potentiation unlike many benzodiazapines.

Hope that helps...Remember kids, eat your grapefruit.

http://www.drugs-forum.com/forum/showthread.php?t=103590

I can find you several on bluelight pointing out the same facts.

How the fuck do they potentiate oxy,

I said depotentiate.

you sir are quite wrong. You obviously don't know what your are talking about because oxycodone is highly.metabolized through cytochrome 450 and tagmet definitely increases the duration of oxy

They decrease oxycodone-oxymorphone conversion by inhibiting 2D6/3A4 respectively. Please try and read and comprehend accurately as I won't repeat my logic again.

From df:

SWIM agrees that cimitidine IS in fact a potentiator to a degree but also an inhibiter of greater levels of euphoria that could be acheived with the combination of a CYP3A4 only inhibitor and a CYP2D6 inducer.

Because Cimitidine is a potent CYP3A4 inhibitor it does potentiate opiates in that it increases the duration through inhibiting the enzyme responsible for eliminating the drug through inactive metabolites (CYP3A4) but because it has the potent ability to drastically reduce the amount of morphine created by codeine, hydromorphone created by hydrocodone, and oxymorphone created by oxycodone via CYP2D6 inhibition it isn't the most suitable potentiator for opiates.

And actually the amounts of active and significantly more potent metabolites of codeine, hydrocodone, and oxymorphone are definately significant especially with codiene which is basically euphorically inactive without being converted into morphine via CYP2D6.

Here are the percentages for the afformentioned CYP2D6 substrates.

Hydrocodone- -Hydromorphone= a maximum yield of 25%

Oxycodone- -Oxymorphone= average yield of 15%

Codeine- -Morphine= average yield of 10%

So with a CYP2D6 inducer thrown into the mix these conversions become significantly higher, conversly, a CYP2D6 inhibitor such as tagamet (cimitidine) would lower the yields of the more potent metabolites created via CYP2D6

I hope that makes sense.
 
Last edited:
Well cimetidine will certainly increase bioavailability and half-life significantly but unfortunately you'll have to sacrifice some potency.

Give it a go, you're the only one who can evaluate its benefit to you. I would suggest you do the same with hydroxyzine because as I mentioned before its inhibition of liver enzymes is mild, it has its own analgesic mechanism, and could add to the sedation of oxycodone therefore increasing relaxation.
Wrong , cimitidine does not increase bioavailability and again you contradicted yourself first you say it increases bioavailability which would essentially increase potency and effects, and then you say tagamet will decrease potency9 you dknt make sense. Next time bring in some sources and facts besides what you believe to be true.

Also, the dude doesn't care about relaxation, he wants pain relief. Pissed me off when you tell me I'm wrong when I'm trying to help someone and all you care about is arguing.


Infrared..
I prefer cimitidine because it inhibits multiple enzymes and isn't as volatile as grapefruit juice. Gfj is alright, but you have to drink multiple cups and sometimes the effects are weaker and other stronger. Oxycodone was my DOC for years and I used to extensively and was very interested in getting more bang for my buck by potentiation. I have utilized both grapefruit juice and tagamet, and tagamet is all around better . It's easy to carry around as they are just pills , it is easy to measure your dose and easy to swallow a pill or two, and IMO/IME tagamet was more effective
 
Again, we are referencing CYP2D6 when it has been established that it is relatively insignificant (because oxymorphone is only 11% of the metabolites of oxycodone). I feel that, maybe, Grapefruit Juice extract is the way to go since it somewhat specifically, inhibits CYP3A4 and not 2D6 (or at least, not a lot).
 
Yah I overreacted, I didn't mean to flip out lol. No hard feelings chrome...

However, I.still stand that oxycodone doesn't need to rely on oxymorphone for effects. The metabolization is so minimal it doesn't really matter. Unlike codeine or hydrocodone, oxycodone has a relatively low(strong) Ki value which is somewhere between 10-20 Nm which means it is quite a potenet opioid
Also another internet forum is not an ideal source , it is more persuasive to post studies and such

Again, we are referencing CYP2D6 when it has been established that it is relatively insignificant (because oxymorphone is only 11% of the metabolites of oxycodone). I feel that, maybe, Grapefruit Juice extract is the way to go since it somewhat specifically, inhibits CYP3A4 and not 2D6 (or at least, not a lot).

Idk how many times I have to say this, oxymorphone has nothing to do or very very very minimal effects felt from oral

http://paincenter.wustl.edu/c/BasicResearch/documents/KharashClinPharm06.pdf


In this link, the experiementers gave subjects a high dose of quinidine , a very potent 2D6 inhibitor, and the effects were relatively the same if jot stronger. From this they concluded that oxynorphone has nothing to do with the effects felt from oxy. In the very last paragraph. The study states that the metabolites did not affect in a good or bad way the effects of the parent drug oxycodone. Finally and most important, the.metabolites of oxy including oxymorphone were barely, if completely not at all, were able to cross the blood brain barrier into the cns. This shows that even if you took a 2D6 inducer with oxycodone ad were a super fast 2D6 metabolizer and were able to produce more than normal amounts of oxymorphone, the oxymorphone wouldn't even be able to pass through the BBB which means you wouldn't feel jack shit from the oxymorph even if you were a freak metabolizer!!!

Point closed
 
Last edited by a moderator:
^ That's one study and done in rats. I would find it surprising that a 15% yield of oxymorphone is negligible. I will attempt to get that study from the user.

As the studies I posted mentioned serum levels of oxymorphone are nearly half of those of oxycodone done in chromotographical laboratories. It would be illogical to ignore that in the same way that codeine-morphine conversion can't be ignored.

several of which are thought to be active metabolites to some extent, although a study using conventional oral oxycodone concluded that oxycodone itself, and not its metabolites, is predominantly responsible for the drug's opioid effects on the brain.[3]

http://en.wikipedia.org/wiki/Oxycodone

The study in rats mentioned is the one you provided.

From the data sheet itself:

Metabolism

Oxycodone hydrochloride is extensively metabolized to noroxycodone, oxymorphone, and their glucuronides. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Oxymorphone, although possessing analgesic activity, is present in the plasma only in low concentrations. The correlation between oxymorphone concentrations and opioid effects was much less than that seen with oxycodone plasma concentrations. The analgesic activity profile of other metabolites is not known.

The formation of oxymorphone, but not noroxycodone, is mediated by cytochrome P450 2D6 and, as such, its formation can, in theory, be affected by other drugs

The two main metabolites are oxymorphone--which is also a very potent analgesic

http://www.ncbi.nlm.nih.gov/pubmed/17525040
 
Last edited:
I don't think that the effects of oxycodone being converted to oxymorphone are negligible at all. When I'd drunk a lot of gfj and took my usual dose of oxy, it was much more intense, euphoric and nod like. It was much like many have reported oxymorphone to be experienced like. It was for me horrible and I didn't like it - but I guess some do.
 
Lolol again, you posted something that proved me right. The correlation between opiate effects and oxymorphone serum levels was much less than that off oxycodone serum levels and opiate effects. If you don't understand, this sentence states that rising or lowering levels of oxynorphone do not correspond with opiate effects which means that oxymorphone has nothing to do with effects of oxycodone. However, the sentence states that rising and lowering levels of oxycodone absolutely affect the effects felt from oxycodone. Once again the sentence shows that production or inhibition of oxymorphpne is exceedingly trivial when dosing oral morphine.

Lolol you are making my job easier...


Synthetix, your experience shows that inhibiting 3A4 increases the effects of oxycodone, nothing more. It's not like you took a 2D6 inducer and felt higher. Your post doesn't prove or disprove that oxycodone relies on oxymorphone for mu agonism
 
^ You need a pair of glasses. If your referring to the data sheet, it clearly states that oxymorphone possesses analgesic effects but lower to that of oxycodone relative to serum levels. Which means that oxymorphone does in fact have analgesic effects and does play a role as a metabolite as well as noroxycodone.

To simplify it for you it's saying:

Oxycodone > Noroxycodone > Oxymorphone

All three are active and that the other metabolites have yet to be determined activity.

What's also interesting is the elimination half-life of oxycodone is 4.5 hours in 12 hour extended release OxyContin tablets. I wonder what's providing analgesia for 7.5 hours.

From Purdue:

The apparent elimination half-life (t½) of oxycodone following the administration of OxyContin was 4.5 hours compared to 3.2 hours for immediate-release oxycodone.

Noroxycodone exhibits very weak anti-nociceptive potency compared to oxycodone, however, it undergoes further oxidation to produce noroxymorphone, which is active at opioid receptors.

Oxymorphone has been shown to be active and possessing analgesic activity
 
Last edited:
I'll stay out of this oxymorphone discussion....

For Cimetidine, how long before taking the opiate should it be ingested?

Idk how many times I have to say this, oxymorphone has nothing to do or very very very minimal effects felt from oral
By the way, I was agreeing with you....
 
Last edited by a moderator:
My issue is that I've only been taking this for 3 weeks and will not likely take it for much longer (ie before my next visit with my doctor). Also, I do not want to take anything stronger/increase dosage because of my fear of withdrawal (which is already going to happen since I have a tolerance). Therefore, I am looking for a way to make the analgesic effects of my current 10/325 percocets last longer.

That's very responsible and aims towards the goal we all should. Sorry, at first I had the impression you were a chronic pian patient. Perhaps skimming through this will offer some other ideas: The Ultimate Opiate Potentiation Thread
 
Okay. No more argument over trivial things that aren't likely to help the OP anyway. No more dicksizing pharmacology knowledge, this is BDD after all. And please try not to pull in sources from other, often less reliable drug forums, unless they are extremely relevant.

Put the OP first. This is fair warning.
 
I'll stay out of this oxymorphone discussion....

For Cimetidine, how long before taking the opiate should it be ingested?


Take 400-600 mgs tagamet 30-60mins before dosong oral oxycodone


Bleh, I'm not going to argue with you chrom, you still have not posted one thing proving that oxymorphone provides essential mu agonism for the effects of oxycodone ...dude posting that oxymorphone is potent has absolutely nothing to do with whether or not oxycodone relies on oxymorphone for opiate effects. You are takkmg those completely out of context lmao. No where in your post do you say anything proving that oxymorphone is the main cause for opiate effects. Yah no duh is oxymorphone potent and a great analgesic. This had been known dude. Like seriously, cmon now ....

And omfg hahahahah, you are so far from being right. The serum levels sentence basically says oxynorphone is more potent on a mg per mg basis. Also just because a drug is active at receptors, doesn't mean that a drug will reach to those receptors after the parent drug is metabolized into such drug. I think you need to get glasses because you obviously aren't reading it correctly or are having trouble understanding what the message is.

Loperamide is active at opiate receptors, but that doesn't mean it will actually get to those receptors and bind to such receptors



Bronson is right, this is my last post in this thread. I was only trying to help the OP so that he could know the actual truth and help him potentiate his oxycodone.


I don't mean to boss you around Bronson, but the OP had his questions answered, if he has any more questions I said he could pm.me. could you close this thread please?
 
No worries moderator, I was actually hoping for a bit of pharmacological and pharmacokinetic discussion.

Also, if I get some information about cimetidine, I will try a bit of a personal trial.

First, I'll try 500mg Grape Fruit Juice extract (tablet) half an hour before oxycodone 10mg by mouth. Then I will try, 6 hours later, 400mg half an hour before oxycodone 10mg by mouth then post results.

Also, what is the half life of Cimetidine and how long does it inhibit CYP450 enzymes? Do you need to take it each time you take oxy, even if it's only 6hrs apart?
The website says: "For relief of symptoms, swallow 1 tablet with a glass of water. For prevention of symptoms, swallow 1 tablet with a glass of water right before or any time up to 30 minutes before eating food or drinking beverages that cause heartburn. Tagamet HB 200® can be used up to twice daily (up to 2 tablets in 24 hours)."

This makes it seem like it will potentiate (read: inhibit enzymatic breakdown) for that long but I do not want to assume...

Thanks
 
Last edited:
TerI already said this, but ill say it again lol :)

Take 400-600 mg tagamet 30-60 mims before your oral oxycodone dose. Nl

Also, if you want to try grapefruit juice to potentiate, the extract is useless. It won't contain the alkaloids you need to inhibit the enzymes. The highest levels of such alkaloids are present in an actual fresh grapefruit, other than that the only way grapefruit will work to inhibit the enzymes would be to drink 100% PURE, NOT from concentrate, WHITE grapefruit juice. Note that white grapefruit juice isn't white, it is more a light pinkish color. You want to avoid the darker, ruby red grapefruit juices as these usually have water and other shit added to them. For the same reason that ruby red or concentrated gfj won't work, the extracts won't either. The good stuff is only found in pure/natural grapefruits
 
TerI already said this, but ill say it again lol :)

Take 400-600 mg tagamet 30-60 mims before your oral oxycodone dose. Nl

Also, if you want to try grapefruit juice to potentiate, the extract is useless. It won't contain the alkaloids you need to inhibit the enzymes. The highest levels of such alkaloids are present in an actual fresh grapefruit, other than that the only way grapefruit will work to inhibit the enzymes would be to drink 100% PURE, NOT from concentrate, WHITE grapefruit juice. Note that white grapefruit juice isn't white, it is more a light pinkish color. You want to avoid the darker, ruby red grapefruit juices as these usually have water and other shit added to them. For the same reason that ruby red or concentrated gfj won't work, the extracts won't either. The good stuff is only found in pure/natural grapefruits

Why would it not contain bergamottin and dihydroxybergamottin since, according to Wikipedia, it "is a liquid derived from the seeds, pulp, and white membranes of grapefruit."
 
Lacster what are you on about. Purdue clearly states its metabolites are active and possess analgesic activity. I can't really say anymore than that.

From my first post I said the potentiation induced by hydroxyzine is due to its anti-histamine effect and only that. Also that its inhibition of enzymes is weak.

I also stated that cimetidine will increase oxycodone serum levels and extend its duration, at the cost of potency, which only requires common sense to be able to understand.

The fact that oxycodone is potent on its own was stated, hence why I didn't label it as a prodrug, but that one can't neglect its metabolites.

I have no issue with a discussion, but please bear in mind that even if your points are valid injecting a juvenile tone to this thread by labeling me as selfish, laughing out loud consistently, writing as if your drunk, and dismissing my statements is not going to serve a purpose to the OP.

It would also be nice to have threads in a professional format so when others read it years later it appears neat and serves a purpose even if there is a debate, instead of looking like two kids poking at each other. All I did was call your post subjective which it was as you were going by your own experiences.

Cool down.
 
Ok agreeing to disagree, now let's stop arguing and taking.over his thread.
 
The OPs questions is mainly answered, and I care not to see anymore of the squabbling. Closed. Questions, PM.
 
Status
Not open for further replies.
Top