Oxycodone Metabolized To Oxymorphone?

[SmilexGwG]

I saw a interesting article a while back on oxycodone being metabolized into oxymorphone and hydrocodone being metabolized into hydromorphone. Obviously not alot of the orginal drug will be fully metabolized but my question is:

Since oxycodones metabolized into oxymorphone via the CYP2D6 enzyme, could a CYP2D6 activator cause more oxymorphone to be formed?

Sorry if this question is stupid or a bit out there, ive been really curious about it lately.

Also im pretty sure this is the right forum but not 100% sorry if this has to be moved

 

[Snafu in the Void]

Since oxycodones metabolized into oxymorphone via the CYP2D6 enzyme, could a CYP2D6 activator cause more oxymorphone to be formed?

I have looked into this and I surely don't know the answer. I assume technically yes, however, by inducing quicker metabolization you would also get less high in general (?)

Even tho it metabolizes to oxymorphone I think most of it gets excreted before it goes back into the brain after the liver.

oxymorphone (opana) itself lasts significantly longer than oxycodone, I think a lot of metabolites are "just for show"

Just my guess.

 

[SmilexGwG]

I have looked into this and I surely don't know the answer. I assume technically yes, however, by inducing quicker metabolization you would also get less high in general (?)

Even tho it metabolizes to oxymorphone I think most of it gets excreted before it goes back into the brain after the liver.

oxymorphone (opana) itself lasts significantly longer than oxycodone, I think a lot of metabolites are "just for show"

Just my guess.

Thats what i thought, maybe it barely even gets metabolized into oxymorphone

 

[Nurse Ratched]

Immunoassays are @MsDiz baliwik or maybe @chinup

 

[MsDiz]

Usually I’d explain it but it’s time for my little chicks to learn to fly.

Here’s a good paper.

Observations on the Urine Metabolic Ratio of Oxymorphone to Oxycodone in Pain Patients

Abstract. The object of this study was to evaluate the metabolism of oxycodone to oxymorphone in a pain patient population using a quantitative liquid chro

academic.oup.com

 

[Nurse Ratched]

Usually I’d explain it but it’s time for my little chicks to learn to fly.

Here’s a good paper.

Observations on the Urine Metabolic Ratio of Oxymorphone to Oxycodone in Pain Patients

Abstract. The object of this study was to evaluate the metabolism of oxycodone to oxymorphone in a pain patient population using a quantitative liquid chro

academic.oup.com

Oh that's right you aren't a mod anymore. So sorry I @ you. Will always think of you as one. Don't be a stranger.

 

[Jabberwocky]

Usually I’d explain it but it’s time for my little chicks to learn to fly.

Here’s a good paper.

Observations on the Urine Metabolic Ratio of Oxymorphone to Oxycodone in Pain Patients

Abstract. The object of this study was to evaluate the metabolism of oxycodone to oxymorphone in a pain patient population using a quantitative liquid chro

academic.oup.com

I will not pretend that I have understood the methods or the math, but paper did alert me to few things. Please correct me if I'm wrong on any points.

1) Metabolism of oxycodone to *(oxy)morphone has much similarity with codeine to morphine metabolism.

2) Oxymorphone can and most of the time does play (significant) role in efficacy of oxycodone.

3) Rapid metabolisers of *codone to *morphone are either:
a) Having overall less benefit from taking oxycodone overall, as *codone is converted to *morphone to quickly and eliminated via that route faster than is the case with people who have regular(normal) metabolism rates.
b) Have greater efficacy from oxycodone as *morphone levels are higher and thus more potent opiod exerts it's effects. It also means that this group potentially have greater risk from developing addiction as *morphone (Opana) is known as an opioid with greater addiction potential, than (in this case) a parent compound.

4) Slow metabolisers are in greater risk for toxicity as parent compound is not eliminated in a efficient (predictable) way and levels of *codone stay much higher and longer which leads to build up (something like what happens with methadone)

5) We don't know how to regulate metabolism from *codone to *morphone in a way that would lead to greater *morphone levels and effects, with not converting parent compound to quickly and thus leading to faster excretion and overall diminishing returns.

6) Even if we did it wouldn't make sense to do it as oxymorphone is easily made and having one opioid molecule in the body is more safe and practical to manage than having two.

5 and 6 are my conclusion that are not talked about in the paper but am trying make a post that is relevant for OP.

Have I got general gist of the paper right @MsDiz ? Can you elaborate further if you have time? I would like to read more posts from you. Thanks.

Edit - edited for spelling.

 

[SmilexGwG]

Usually I’d explain it but it’s time for my little chicks to learn to fly.

Here’s a good paper.

Observations on the Urine Metabolic Ratio of Oxymorphone to Oxycodone in Pain Patients

Abstract. The object of this study was to evaluate the metabolism of oxycodone to oxymorphone in a pain patient population using a quantitative liquid chro

academic.oup.com

Will read this, thanks

 

[SmilexGwG]

I will not pretend that I have understood the methods or the math, but paper did alert me to few things. Please correct me if I'm wrong on any points.

1) Metabolism of oxycodone to morphone has much similarity as codeine to morphine.

2) Oxymorphone can and most of the time does play (significant) role in efficacy of oxycodone.

3) Rapid metabolisers of *codone to *morphone are either:
a) having overall less benefit from taking oxycodone overall
b) have greater efficacy from oxycodone as *morphone levels are higher and thus more potent opiod exerts it's effects. It also means that this group potentially have greater risk from developing addiction as *morphone (Opana) is known as an opioid with greater addiction potential, than (on this case) a parent compound

4) Slow metabolisers are in greater risk for toxicity as parent compound is not eliminated in a efficient (predictable) way and levels of *codone stay much higher longer which leads to build up (something like what happens with methadone)

5) We don't know how to regulate metabolism from *codone to *morphone in a way that would lead to greater *morphone levels and effects, with not converting parent compound to quickly and thus leading to faster excretion and overall diminishing returns.

6) Even if we did it wouldn't make sense to do it as oxymorphone is easily made and having one opioid molecule in the body is more safe and practical to manage than having two.

5 and 6 are my conclusion that are not talked about in the paper but am trying make a post that is relevant for OP.

Have I got general gist of the paper right @MsDiz ? Can you elaborate further if you have time? I would like to read more posts from you. Thanks.

This helped alot,

 

[Jabberwocky]

This helped alot,

Hold on there - I am not sure have I got things right. I'm trying to understand but am not nearly educated enough to read articles like this one. Actually I'm trying to get MsDiz to stick around a bit more with the intention she will stick around even more after that and get into vicious cycle of posting on BL again.

 

[Jen X]

You can do a ton of hydrocodone and it will never feel like hydromorph. Hydromorph is the closest feeling to heroin you can get. Hydrocodone is very weak in comparison

 

[Jabberwocky]

You can do a ton of hydrocodone and it will never feel like hydromorph. Hydromorph is the closest feeling to heroin you can get. Hydrocodone is very weak in comparison

OP is asking about oxycodone and oxymorphone as oxymorphone is metabolite if oxycodone. Neither of those 2 is weak opioid thats for sure.

 

[Jen X]

OP is asking about oxycodone and oxymorphone as oxymorphone is metabolite if oxycodone. Neither of those 2 is weak opioid thats for sure.

They also mentioned hydrocodone and yes oxycodone is a weaker opioid compared to hydromorph oxymorph fentanyl etc... i've been addicted to all for 10 or so years.

 

[Jen X]

And same with oxycodone to oxymorph, you would OD on oxycodone trying to get an oxymorph high. It's metabolized in very low quantities

 

[Las Veghost grower]

And what’s the deal with metabolism…

jerry seinfeld stand up - Google Zoeken

 

[HOOH]

Does anybody know why oxycodone is active in of itself yet codeine needs to metabolized to morphine first, despite the fact that both of them have a "blocked" hydroxyl group

 

[Jabberwocky]

And same with oxycodone to oxymorph, you would OD on oxycodone trying to get an oxymorph high. It's metabolized in very low quantities

Having read the paper posted by MsDiz for a second time, I'm not sure that this is the case. Maybe I am reading it wrong and "fast metabolisers" do not get benefit in any outcome, but from what I could gather there is a subgroup that converts codone to morphone in such a way that they actually get high amounts of morphone circulating in the bloodstream end exerting effects. This is only a subset of people, but if I am reading it right, there are people who convert enough codone to morphone (and not exerting morphone too fast) so they experience what you expressed as "oxymorphone high". Those people would be the ones really liking the oxycodone similarly to people who covert codeine into morphine in high amount(ratio). I am not sure is what I am writing actually what can be read from paper or is converting oxycodone to oxymorphone always a one way street to only faster elimination. That part confuses me and I would like if @MsDiz could just shortly explain that part.

 

[MsDiz]

Oh bless you all!! Haha!!

I will come on later and explain it better. I honestly thought that paper was more user friendly than it actually is.

It’s nearly 2pm now and I’ll be on around 9pm.

 

[Jabberwocky]

I honestly thought that paper was more user friendly than it actually is.

Maybe paper is user friendly but the user is pretty science naive...

Glad to read you later.

Edit -> MsDiz I am volunteering to be a "cleaning assistant" (gotta have some fancy title ) in your future lab. Just to be able to learn about pharmacology and chemistry (I believe that I could upgrade my math pretty quickly). I know you will say yes, so can you recommend some books for pharmacology and chemistry. Like "Biology, pharmacology and chemistry for dummies"? Or if I want to be more serious - "Pharmacology 101". I'm not even kidding. Ok, I will not pressure you about lab, but can you give some directions for a person that has only high school and wants to learn pharmacology and chemistry? I guess that this is a PM question.

 

[4meSM]

Does anybody know why oxycodone is active in of itself yet codeine needs to metabolized to morphine first, despite the fact that both of them have a "blocked" hydroxyl group

There are a few structural characteristics which define whether a morphinian is going to be (significantly) active by itself or not. in the case of oxycodone it's due to having a carbonyl group at C6 + a simple (saturated) bond between C7-C8 + a hydroxy group at C14 (codeine has neither of those things). All of which seem to increase activity in a very big way.

So a "blocked" hydroxy group (phenol) at carbon n°3 doesn't automatically kill the activity, it just decreases it. But it does have a pretty big advantage as well: it usually makes the drug more orally bioavailable.
This may be one of the reasons why doctors tend to prefer codeine, hydrocodone and oxycodone over morphine, hydromorphone and oxymorphone (but it's mostly due to the fact that they're perceived as being less "abusable").
In the case of heroin, the acetyl group does "block" the phenol as well, which actually makes the drug almost completely inactive (but also more lipophilic). However, that particular ester group gets broken down very quickly upon entering the body, so heroin ends up being a very effective pro-drug for 6-monoacetylmorphine which is a potent opioid.

I made a quick summary of the main structural things that tend to modulate the opioid-like activity of those drugs. Obviously it isn't 100% complete and there are exceptions.
Green= increases activity
Red= decreases activity

Spoiler: Main examples

Spoiler: And here is oxycodone's metabolism

source: https://www.pharmgkb.org/pathway/PA166170927