When benzos (and other drugs) are present they competitively inhibit the first pass metabolism of Naltrexone to its much longer lasting metaboite 6-β-naltrexol.
Virgil cited this study: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2014407

This is a completely different issue than what has been raised here before about nal and benzos and gaba receptors.

I've put together some graphical representations of a few scenarios involving a couple benzos and some other drugs:

This is a lab test where serum levels of Naltrexone and 6-β-naltrexol were measured following a 100 mg dose:


These are some drugs and the degrees with which they inhibit the first pass metabolism of Naltrexone:


This is what normally happens when you take a 50 mg dose of Nal (although there are wide individual differences in metabolism):


Nal+Diazepam:


Nal+Temazepam:


Nal+Corticosterone:


Nal+Testosterone (At 10x natural plasma levels):


The moral of the story: Don't do roids!

That's my main question AJ and I was hoping you specifically could help me with that. Because if it did, these graphs would look dramatically different, in fact increasing the therapeutic effect of Nal+whatever as opposed to decreasing it.

To answer your first question...I don't know, doesn't it get excreted by the renal system unchanged (at least partially)? If you can explain it to me then I can make the graphs reflect that. I'm positive it has to go back through the hepatic system in order to reach the renal system at least somewhat...insights welcome. ?

edit: the numbers were talking about here don't negatively affect our major concern on this board which is:
Q: Does Benzo use affect The Cure?
A: No, not from this angle

After reviewing what you and I just wrote (me drunk ) I think that first pass metabolism is much more significant than you or I were thinking it was.

In first pass metabolism:

Drug-->goes through stomach lining--->into (that main vein in the) liver--->into bloodstream

from there it's game on (save the blood brain barrier, which nal and 6bnal cross readily)

and it stays attached to receptors in the brain and stomach/intestine linings for a good period of time.

diffusion by the renal system accounts for most of the plasma reduction at this point...I think...metabolization by the hepatic system is minor because almost none of it passes through there anymore.

please correct me if I'm wrong, I've absolutely no education in this area, I'm just guessing. But it does seem to line up with what the actual measurements suggested, in I think, the first figure I posted in this thread. ty AJ

I based my :

"Ratio of Metabolites After First Pass (Nal/6-β-naltrexol)" Number on what was actually observed in this figure:


I wish I had better data but it isn't to be found.

Despite all of the other insignificant metabolites the actual ratios or quantities present seem to mimic, quite homogenously the graphs I've already presented above.

If you could (and you can if you want) re-make the images I've presented above with more accurate estimates then I would have already done it. And I've already fooled around with the numbers to see if there was anything notable.

[ok totally wasted now, gonna have to get back to you in the morning--i'll edit this post later. thank you aj for even you're remote consideration.] -E

yeah I'll edit this post too

I'll read what you're trying to tell me...in the morning. Gimme a break eh?

Could I just send you this spreadsheet? So you can edit it?

So that I can see what you're thinking?

I think the spreadsheet I made could illustrate that.

It would result in ridiculously long 6bN levels though. Like...for days. Is that what actually happens?

Lo0p,

In your first post of this thread, you have provided a link to the paper that I cited on the Benzo Bunch thread. Unfortunately, the link you have provided does not work. Check it out and you'll see what I mean. Perhaps you wouldn't mind editing it.

Thanks a lot.

V.

Hi Lo0p,

I don't believe the above conclusion to be strictly true. The paper states "Because of weak or absent inhibition of 6β-naltrexol formation by nicotine, the benzodiazepines (with the possible exception of diazepam), and other opioid compounds, there seems little likelihood of drug/drug interactions occuring in vivo between naltrexone and these drugs". [My italics]

V.

Wouldn't all of these things be accounted for in the published half lives of Nal and 6-b-nal (4h and 13h)? I'm assuming those are based on measurements...right?

I'll look at everything else you wrote later on tonight, I've gotta run off and get some work done. Virgil I'll get back to you too.