OxyContin, grapefruit juice and Plugging.

[Rusty8155]

Hey all new to this...... I have been looking through alot of stuff on here and what he has come to is that I think plugging is the best for taking my OxyContin and geting the most most of it. I have also herd that grapefruit juice will help with the high, but what I want to know is dose the grapefruit juice work the same if your plugging oxy or if your taking the juice would it be better to take it orally because the juice would make it stronger ?? Thanks guys hope I don't get yelled at

 

[Pilll_head]

You don't have to use SWIM here. I've never plugged anything but the grapefruit juice will still help. It delays metabolism, so you won't experience a higher high, but it will last longer, although I don't know how much of an improvement you actually get on a controlled-release formulation. I have switched to Tagamet recently (600 mg, 1 hr before) and gotten the same results without having to drink the nasty juice.

 

[Horrux]

I think you will get a greater high between GFJ/no GFJ orally, but only a longer one between these 2 options when plugging. The reason being that by plugging, the Oxy makes it into your blood before any metabolism happens, whereas orally, metabolism already happens before it hits the bloodstream. So, the max blood concentration will be increased by the pre-dosing of GFJ if the drug is administered orally, but not if it is administered any other way (railing, for example). However, metabolism is slowed down in all cases of GFJ administration. Which works for most drugs, actually.

 

[jones-in_J]

Hey all new to this...... Swim has been looking through alot of stuff on here and what he has come to is that he thinks plugging is the best for taking his OxyContin and geting the most most of it. He has Also herd that grapefruit juice will help with the high, but what He wants to know is dose the grapefruit juice work the same if your plugging oxy or if your taking the juice would it be better to take it orally because the juice would make it stronger ?? Thanks guys hope I don't get yelled at

At first I thought you were asking if you should put the grapefruit juice in your ass. I hope I was originally wrong and am right re-reading it and thinking otherwise 8(

 

[Swimmingdancer]

Hey all new to this...... Swim has been looking through alot of stuff on here and what he has come to is that he thinks plugging is the best for taking his OxyContin and geting the most most of it. He has Also herd that grapefruit juice will help with the high, but what He wants to know is dose the grapefruit juice work the same if your plugging oxy or if your taking the juice would it be better to take it orally because the juice would make it stronger ?? Thanks guys hope I don't get yelled at

At first I thought you were asking if you should put the grapefruit juice in your ass. I hope I was originally wrong and am right re-reading it and thinking otherwise 8(

That's what I thought too! Then I re-read it and thought maybe he/she is just asking if they should just take the Oxy orally with grapefruit juice as opposed to plugging the Oxy? Wikipedia says that the bioavailability of oral administration of Oxycodone averages 60–87% with rectal administration yielding the same results. Do people on here report stronger effects from plugging it, or is it just done for a faster onset? I would assume that with rectal administration that grapefruit juice would not act as a potentiator, because the way that grapefruit juice affects oxycodone metabolization is through the liver - grapefruit inhibits the production of the enzyme which breaks down Oxycodone. If you are taking it rectally it should bypass the liver and go directly into the bloodstream, so enzyme inhibition wouldn't affect it. Now personally I don't find that I notice any difference when I take drugs with grapefruit juice, but some people do find it to make a noticeable difference. So, assuming that the oral and rectal BA are the same, and you were hoping to get stronger or longer effects, then that would mean that it would actually be better to take it orally with the grapefruit. If you are looking for faster effects, then plugging would probably be better.

I think you will get a greater high between GFJ/no GFJ orally, but only a longer one between these 2 options when plugging.

Why would drinking grapefruit juice when plugging Oxy make the Oxy last any longer?

 

[effie]

I'm not sure if plugging oxycodone gives a noticable advantage over oral administration or not; it may well kick in faster though.

The idea behind GFJ is that it inhibits several CYP enzymes including CYP2D6 which is responsible for metabolising oxycodone. If you inhibit it's metabolism, then plasma concentration will remain higher for longer. However, one of oxycodone's metabolites is oxymorphone, which is active and stronger than oxycodone, and production of this will be reduced by consuming GFJ. I am not sure how significant it is, but it is something to bear in mind especially if GFJ doesn't seem to be potentiating the effects at all..

 

[Horrux]

Why would drinking grapefruit juice when plugging Oxy make the Oxy last any longer?

The liver filters your blood. Yes, there is blood flow to your liver directly from your intestines, where orally administered substances are absorbed, but your liver also filters blood that does not come straight from your intestines. As such, given that most drugs are metabolized at least in part in the liver, GFJ, citrus bioflavonoids or other CYP inhibitors will, generally speaking, give you greater or longer-lasting drug effects than without. This is valid for stuff you smoke, inject, plug, rail, eat, whatever.

There are exceptions to this however, and I don't know what they might be. I just tend to have my cyp inhibitors to make sure I get the most out of my drugs.

 

[Swimmingdancer]

Oh thanks for explaining, that's an interesting idea, I always thought that the grapefruit only had a significant effect on first-pass metabolization by the liver from the digestive system.

Do you find it to make a noticeable difference for you?

 

[Horrux]

Oh thanks for explaining, that's an interesting idea, I always thought that the grapefruit only had a significant effect on first-pass metabolization by the liver from the digestive system.

Do you find it to make a noticeable difference for you?

Please explain what you mean by "first-pass"... There seems to be a great deal of confusion with regards to a difference between liver treatment of blood from the intestines and blood from general circulation being what is meant by "first pass", whereas I do believe it is referred to the oxidation phase of drug metabolism, which should be followed by the conjugation phase. The second can usually not happen without the first. Your question confuses me.

 

[Swimmingdancer]

Please explain what you mean by "first-pass"... There seems to be a great deal of confusion with regards to a difference between liver treatment of blood from the intestines and blood from general circulation being what is meant by "first pass", whereas I do believe it is referred to the oxidation phase of drug metabolism, which should be followed by the conjugation phase. The second can usually not happen without the first. Your question confuses me.

http://en.m.wikipedia.org/wiki/First_pass_effect

 

[Horrux]

http://en.m.wikipedia.org/wiki/First_pass_effect

OK. This is sometimes confused with the 2-phase drug metabolism that happens in the liver.

With regards to first pass or not, the 2-phase metabolism of a drug is what it is. The CYP inhibitors (GFJ) are effective on the first phase of all drug metabolism, first pass or not.

 

[Pilll_head]

I'm not sure if plugging oxycodone gives a noticable advantage over oral administration or not; it may well kick in faster though.

The idea behind GFJ is that it inhibits several CYP enzymes including CYP2D6 which is responsible for metabolising oxycodone. If you inhibit it's metabolism, then plasma concentration will remain higher for longer. However, one of oxycodone's metabolites is oxymorphone, which is active and stronger than oxycodone, and production of this will be reduced by consuming GFJ. I am not sure how significant it is, but it is something to bear in mind especially if GFJ doesn't seem to be potentiating the effects at all..

I think you meant CYP3A4, that is the one that converts oxy and hydro to an inactive metabolite, that's what GFJ primarily inhibits. The only time you care about CYP2D6 inhibition is if you are taking codeine which is metabolized by CYP2D6 to morphine. If that is inhibited, you won't get any buzz or pain relief

 

[Misfit Chick]

I find this interesting, however, i cant fit a grapefruit up my ass.

 

[Swimmingdancer]

OK. This is sometimes confused with the 2-phase drug metabolism that happens in the liver.

With regards to first pass or not, the 2-phase metabolism of a drug is what it is. The CYP inhibitors (GFJ) are effective on the first phase of all drug metabolism, first pass or not.

Ah, thanks, that makes sense. What I meant was that I had heard it didn't really make a noticeable difference if you were using an ROA that bypassed first-pass metabolism, because during first pass CYP inhibition makes a much bigger difference, but it makes sense what you said about it potentially making the effects of the drug last longer but not stronger.

I think you meant CYP3A4, that is the one that converts oxy and hydro to an inactive metabolite, that's what GFJ primarily inhibits. The only time you care about CYP2D6 inhibition is if you are taking codeine which is metabolized by CYP2D6 to morphine. If that is inhibited, you won't get any buzz or pain relief

That's a very good point and is mostly correct, I'm sure Effie meant to say CYP3A4. But not everything you said is 100% correct.

Oxycodone is deactivated by CYP3A4 (and CYP3A5) so CYP3A4 is of primary concern when it comes to oxycodone.

As for codeine, it is activated to morphine by CYP2D6, but it is also activated by CYP3A4 into codeine-6-glucuronide which is responsible for a large percentage of the analgesia. So inhibiting CYP2D6 would decrease the "buzz" and the analgesia, but not eliminate analgesia. One wouldn't want to deliberately take any CYP2D6 or CYP3A4 inhibitors with codeine, although taking one or the other should not make codeine completely ineffectual.

In addition, codeine is not actually the only opioid where we have to worry about CYP2D6. Tramadol is converted by CYP2D6 to its most active metabolite, O-desmethyltramadol, which is way stronger and longer-lasting than tramadol. So with tramadol we do not want to inhibit CYP2D6. Hydrocodone is also activated by CYP2D6 to hydromorphone. so again CYP2D6 inhibitors are undesirable with hydrocodone.

But what confuses me about tramadol is that it is available for injection (unlike codeine), which to me does not make sense, why would anyone want to inject tramadol when it appears that would make it much less effective?

Oxycodone is metabolized by CYP3A4, CYP3A5 and CYP2D6. Oxycodone is deactivated by CYP3A4 and CYP3A5 to noroxycodone and activated by CYP2D6 to oxymorphone. Oxycodone itself is believed to be responsible for much of its effects, however since we know hydromorphine is active, would it be safe to assume that inhibition of CYP2D6 would decrease the metabolization into hydromorphone and therefore be undesirable?

TLDR; version - Don't take CYP2D6 inhibitors with codeine, tramadol, or hydrocodone. Taking CYP3A4 inhibitors (such as grapefruit) with most other opioids can make the effects stronger and/or longer. Question: why is tramadol available for injection?

 

[Horrux]

^^^
What makes you think metabolism is any different for an injected drug than for an orally-administered one, except for the first-pass effect?

The way you are writing, it's like you think some liver enzymes are only present in the first-pass effect... I don't think there is any evidence of that anywhere.

 

[Swimmingdancer]

^^^
What makes you think metabolism is any different for an injected drug than for an orally-administered one, except for the first-pass effect?

The way you are writing, it's like you think some liver enzymes are only present in the first-pass effect... I don't think there is any evidence of that anywhere.

I do not think that and I never said that. The only thing I said on that subject was that I had heard that enzyme inhibition made a bigger difference when drugs were administered orally because the first-pass is where a lot of the drug is normally deactivated (although not for all drugs of course). And it is very accurate that drug metabolization is different depending on the ROA, not because the enzymes in the liver are any different, but because the first-pass has a huge effect on drugs before they reach the brain/body. The ROA makes a big difference for certain drugs, for example pro-drugs that are changed into their active metabolites by the liver, or for drugs like heroin, which is entirely converted to morphine by means of first-pass metabolism, resulting in deacetylation when ingested, whereas if it is injected it is able to reach the brain before that happens.

In addition, non-oral ROAs avoid the digestive system, including acids in the stomach and enzymes in the gut. Interestingly, I just found a study that seems to show that grapefruit affected enzymes in the intestine differently from enzymes in the liver.

In hepatic (liver) microsomes, bergamottin (the furanocoumarin isolated from grapefruit juice) treatment for 10 days reduced (inhibited) the activity of CYP3A12 by 50% and CYP1A1/2 by 75%; CYP2B11 activity was moderately induced. In jejunal (small intestine) microsomes, CYP3A12 activity doubled with bergamottin treatment; CYP2B11, CYP1A1/2 activity was not detected. In conclusion, bergamottin is both an inhibitor and an inducer of P450 enzymes.
http://www.ncbi.nlm.nih.gov/pubmed/11792681