Buprenorphine, first pass metabolism

[Kewlwip]

I'm interested in Buprenorphine to Norpbuprenorphine.

I've read that Bupe goes through N-dealkylation, mediated by the P-450 3A4 isozyme to become Norbuprenorphine, and also is eliminated through glucuronidation.

Through which pathway does first pass metabolism favor? Would taking Bupe orally result in more Norbupe?

Also, are there any safe, obtainable P-450 3A4 isozyme inducers?

 

[paper planes]

ive read that takin orally it has a very low bio-availability..and as far as inducer of the p-450 grapefruit juice and st. johns wort seem to be the most popular

 

[Kewlwip]

I know "Buprenorphine" has a low bioavailability orally. I don't want Buprenorphine, I am interested in Norbuprenorphine.

If 90% of Bupe is metabolised when taken orally, is that increase all because of glucuronidation?

Or is it because of more N-dealkylation? In which case you would end up with more Norbupe, right?

And I think grapefruit juice is an inhibitor, it would potentiate Buprenorphine, but I don't want that.

I have heard St. John's Wort is an inducer though.

 

[sekio]

I think the metabolism favours N-demethylation to norbupe first, but that pathway can get easily saturated (has a low "ceiling dose" - at higher doses the "apparent" bioavailiablilty of buprenorphine vs norbupe goes up)... Norbupe is glucuronidated anyway.

http://dmd.aspetjournals.org/content/12/5/577.abstract

There are no effective p-450 enzyme inducers that don't produce wacky other side effects (and are availiable easily). Modafinil and SJW are the only 2 I would reccomend but even then, there's no guarantees.

 

[Kewlwip]

Thank you Sekio.

 

[jaysofab]

Question do you take your sub or sjw first and I have a theory if you take suboxone orally with sjw maybe it would metabolite better?