Rectal absorption of gabapentin

[Jamshyd]

From some random forum I found on the internet:

I believe the answer is that gabapentin is a zwitterion sp? and therefore
is actively transported across the gastrointestinal tract. Since the active
transporters are not present in the rectum, adsorption is practically nil.

Now, with that said we did have an end stage head neck cancer patient with
neuropathic pain. As I recall we upped his dose from 100mg
tid to 300 or 400mg tid rectally ( I believe I just compounded a suspension
and it was given as an enema). I followed up after about 3-4 days of
administration to see if we should continue. According to the nurses the
suspension was working and continuing to relieve the patient's pain as well
or better than the original oral dose. Who knows, could have been placebo,
could have been effect of other meds (although none changed during this
time period), anyway not very scientific evidence.

So, in answer to your question there is no literature supporting the use of
gababpentin rectally. But, it may be possible to titrate to a high enough
dose to have some benefit.

Can anyone comment on that?

Also, can anyone here elaborate on Zwitterons? What other drugs are classified as such?

 

[kidamnesiac]

psilocybin (psilocin at the right pH)
I doubt it has anything to do with absorption, personally.

 

[Jamshyd]

Ok... but please elaborate?

 

[fastandbulbous]

Well if it's in an ionized state, it isn't going to cross a cell membrane or gut wall without either active transport of facilitated diffusion coming into play (facilitated diffusion uses carriers, but in a passive manner. It cannot go against a concentration gradient the way active transport can) and considering that except for a narrow pH range it'll be either an anion or cation, that rather buggers absorvtion of zwitterions without a mechanism to transport it across the membrane (or forms micells in aqueous soln & can be absorbed via a fat medium.

The best & most common example of zwitterions are amino acids. At their isoelectric point (pH at which they are not ionized as either a COO- or NH3+ ion) their solubility drops off dramatically. This isn't true of all zwitterions though

 

[kidamnesiac]

ive seen many reports of you putting things in your bum that have a primary amine on them and many statements as to how it is absorbed 2-3X more efficiently this way. A primary amine has a pKa of 9-11 and there aint nowhere in the body with a pH that high, hence it will always be ionized. unless there is an active alkaloid transporter...
You said it perfectly, molecules wont cross a membrane except against a concentration gradient. and since there is no gabapentin in your bottom area, osmosis will draw that bugger right across the membrane and into the blood. passive diffusion will let lots and lots of things into your bloodstream if it is water soluble and if it's charged, it probably is water soluble.

btw, i may be wrong (as i have a nasty little fever thats making me see funny), but there is no point at which an amino acid has no charged groups. the pI simply represents the point at which there is no NET charge, ie, the amine is protonated and the carboxylic acid deprotonated, thus, the negative "negates" the positive. this is actually the point at which the two groups are charged as much as possible, relative to the other. (this is a really crappy explanation but I don't want to go into the population/statistical reality of the argument wikipedia probably serves it justice)

 

[fastandbulbous]

Oh, I always took it that the isoelectric point was when it wasn't ionized considering that amines & carboxylate groups are in equilibrium between their ionized and unionized form and at certain pH values the unionized form would predominate. If that's the case I'll have to turn it into a mantra to get it to stick!


Heres a description from a web site that is the sort of thing that got me thinking that way (totally unionized molecule)-

The notion that some ampholytes may pass with changing pH through a state of zero charge (zero zeta potential) on their way from the positively to the negatively charged state has become so useful for specifying and handling polyampholytes that it was extended to all kinds of colloids

 

[kidamnesiac]

the zero zeta potential part means it wont move in an electric field, which is the basis of isoelectric focusing.
If you think about it, most pI's for the AA with uncharged R groups is around 6. At this point, you know the amine is protonated and the acid is not.
Like your quote says, at around pH 6, 99.999% of the amine groups in solution are protonated, 99.999% of the acid groups are not. pH 7 is around 99.99% positive, 99.9999% negative. It is simply where the populations are equal.

 

[Jamshyd]

To be honest, I still don't understand the chemistry being discussed here.

But re: the topic at hand, my personal experience with rectal gabapentin is very difficult to judge, since this drug is simply a mood-stabelizer for me.

 

[kidamnesiac]

I asked a person who works on drug delivery today and he said it should not matter that there are no active transporters in the rectum, esp with molecules under 500 Daltons, as they are readily absorbed through the lumen anyway.
Sorry for not helping you with your chemistry woes. I am not sure what makes the doctor in your quote think that a zwitterion would not be absorbed in the rectum as it would still be a water soluble, polar molecule at physiological pH. Maybe he had the same misunderstanding as f&b, it is easy to misunderstand things like zwitterions if you don't deal with them a lot (I do).
Looking up zwitterion and isoelectric point on wikipedia may help you with some of your chemistry woes. Otherwise, ask specifically what it is you don't understand and I will do my best to help