Tramadol pharmacodynamics and CYP2B6 inhibition (not CYP3A4)

[crOOk]

So I'm a huge fan of Tramadol and stumbled upon this:

Note: Depicted are only the liver enzymes, not those cytochromes that are secreted into the GI tract or any other influences on the pharmacodynamics of Tramadol.

Both these CYP3A4 and CYP2B6 will increase the effects and the duration of a given Tramadol dose.

We all know how to inhibit CYP3A4, but how about inhibiting CYP2B6? Curcumine seems to be the most effective and easily available substance to do this. Has anyone ever tried it? I am getting over 100g 95% curcumine tomorrow morning (morning express delivery tehehehe) and will report back.

Also, does anyone know if there are ways to inhibit UGT2B7 or UGT1A8? I am just curious and not planning to do this since these enzymes (glucuronosyltransferases to be more precise) process some nasty exogenous and endogenous substances like bile acids and both male and female sex hormones (wouldn't want to eat soy on them^^). On top of that it would simply increase the duration which I am not interested in.

More importantly how dangerous would this be regardless of dietary restrictions, in other words only in respect to endogeous chemicals?

On a sidenote, it has been found that Tramadol occurs naturally in clinically significant amounts with concentrations of over 1% in the root bark of a tree that grows somewhere on the African continent. I am too lazy to provide the source, but it has apparently been used to treat pain and diarrhea for centuries by the tribes that had access to the tree and necessary information. I found this very interesting since it once again demonstrates how many natural remedies beyond those that we have already discovered contain substances of potential clinical importance!

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918523/
^Some further info on curcumin, it's a free review. All I can say is 'WOW'! It seems to have received attention by the science community in the last few decades but I hadn't heard of it. I had no idea how many clinically significant beneficial effects it has. Totally gonna slam it now.

 

[crOOk]

Fucking crap. I might not be the ideal person to try this. I just realized that Bupropion significantly inhibits 2D6. The degree of inhibition will bring an extensive metabolizer down to the metabolic rate of a poor metabolizer. Argh.

However, the study I am referring to took the DXO/DXM ratio after oral administration of DXM as the only indicator of the degree of CYP2D6 inhibition. Fortunately both Tramadol and Bupropion are CYP2B6 substrates, so they might compete for it resulting in an attenuation of the slower metabolization rate of Tramadol by CYP2D6... Maybe. I'm so pissed now. Tramadol is among my absolute favourite opiates when my enzyme situation is right and I just allowed myself the luxury of taking for the upcoming 5 days or so. This blows so hard.

Also, I might inject a (microfiltered) solution of the curcumine, since it has very poor bioavailability. Just gonna have to figure out the dosage.
(EDIT There is a lot of CYP3A4 in the intestines which means that Tramadol undergoes intestinal first-pass metabolism. It would be wise to at least eat a certain amount for the potentiation attempt, but use it intravenously for other purposes. I am not sure though if parenteral delivery would supply intestinal mucosal cells with sufficient curcumin to reach maximal inhibition (or get close to it) of intestinal CYP3A4 (at reasonable doses) and thereby prevent it from being excreted or be effective after it is excreted. I'm still pretty sure that oral use will significantly increase the inhibitory effects on CYP3A4 of parenteral curcumin since a lot of the enzyme is already present when the oral drug which action should be modified is entering the intestines.

EDIT: Lol the Lamotrigine I am taking inhibits glucuronosyltransferases, two of which metabolize O-Desmethyltramadol (the good one). This should cause the effects to decrease in duration (it usually lasts 15-20h for me). It also slightly induces CYP3A4 (seemingly not significantly so). So much luck at once!! I guess I am at least gonna skip my Bupropion this week. :D

I think there should be an extensive thread about Tramadol pharmacodynamics and which food/meds can influence it. Looking forward to trying curcumin!


Comprehensive article about first-pass metabolism in the intestine:
http://pharmrev.aspetjournals.org/content/51/2/135.full.pdf

And one about the paradoxical effects of P-GP inhibitors on Tramadol activity and the pH-dependence of Tramadol's intestinal absorptive flux (100% higher at physiological pH over slightly sour one):
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774482/

Ironically, bupropion also seems to inhibit P-GP... lol

 

[Professer]

I enjoy tramadol too. Thanks for all this delicious info.

 

[Hammilton]

The plant you refer to doesn't actually contain tramadol, subsequent follow up study found that it was the result of over medicating cattle who then urinate medication-laden piss all over Africa.

 

[Professer]

^Glad to have that cleared up. I was supprised to first read of it before. Seems logical.

 

[crOOk]

The plant you refer to doesn't actually contain tramadol, subsequent follow up study found that it was the result of over medicating cattle who then urinate medication-laden piss all over Africa.

ROFL! That is fucking hilarious.
Omg I'm lmao here. If you had any idea how many people I've told this...

Got the link for me? Soz, but I really gotta see some proof. :D

 

[sekio]

Here you go

 

[SlidingDown]

Please we do need more Information on tramadol and potentiators and maybe posted in a different forum written for those non-scientifically proses.