oral bioavailability of diacetylmorphine?

[theWorldWithin]

As I understand it the first preperations of heroin sold to the public were in oral form, what was the point of this? I was under the impression that the acetyl groups were lost during first pass metabolism reducing all heroin to plain morphine. Is this not true? Does Diacetylmorphine have a greater oral bioavailability with potentiators such as enzym inhibitors or is it the same as morphine reguardless?

 

[johanneschimpo]

Everything I've ever read confirms what you said, that oral heroin is essentially just oral morphine. Its converted in the body to morphine within minutes.
As for why it was sold in tablets, as opposed to just selling morphine, well, back in the early 1900s they probably didn't realize that plain old morphine would have had the same effect, because they knew that heroin was much stronger than morphine in all other M(ethods)OA.

 

[theWorldWithin]

Alright, thanks johanneschimpo. Also it is my suspicion that enzym inhibition would have no effect on the hydrolosis of heroin to morphine but is there some other potential benfit to this? I doubt it but I am just asking out of curiosity because of how prevelant oral heroin was for such a long time.

 

[Pegasus]

Doesn't diacetylmorphine convert also into 6- and 3- monoacetylmorphine? (6-MAM being the stronger active metabolite)

 

[Dolomiti]

Oral heroin is probably slightly stronger than oral morphine. Why would it *all* turn into morphine before reaching the brain?

 

[theWorldWithin]

To my understanding in the body hydrolysis occures within a few minutes, it would all be converted to morphine before even making it to first pass metabolism, let alone any heroin surviving first pass.

 

[nuke]

Oral diacetylmorphine (</=600 mg) yielded negligible systemic diacetylmorphine and monoacetylmorphine exposures but was associated with linear kinetics and high bioavailabilities for morphine (67% +/- 19%), morphine-3-glucuronide (205% +/- 52%), and morphine-6-glucuronide (180% +/- 61%). In addition, oral diacetylmorphine was absorbed more rapidly and to a greater extent than a concomitant test dose of morphine-d3. CONCLUSIONS: On the basis of the linear pharmacokinetics, the high bioavailability of intramuscular diacetylmorphine, and the rapid and extended morphine absorption from oral diacetylmorphine, the intramuscular and oral routes can be recommended as safe and feasible alternatives to the intravenous route for medical prescription of diacetylmorphine.

Clin Pharmacol Ther. 2003 Oct;74(4):341-52.

It seems as if oral diamorphine acts as some sort of extended release morphine..

 

[theWorldWithin]

Interesting, thanks nuke. Then it seems that diacetylmorphines greater bioavailability more than justifies the cost of its manufacture for pharmaceutical companies versus morphine. Just a few more steps and they gain a far more profitable substance for little added production cost. No wonder it was so widely used before heroins social stigma and scheduling.

 

[haribo1]

I think diamorphine pastils would have been absorbed, at least partially, by the buccal route. I can also confirm that in the UK, Brompton Cocktail is still used for people with terminal illnesses.