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Drug solubility: neither water or fat soluble?

R

Regenesis2

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Jan 4, 2011
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If a drug is neither fat or water soluble, how does your body process and excrete it? I've read about drugs that have solubility only in odd substances like chloroform, methanol, etc.
 
Drugs have to be either fat or water soluble or they're not adsorbed. e.g. lead sulphate and some mercury salts are not water/fat soluble and therefore are much less toxic then you'd expect.

A good rule of thumb is: if it's soluble in chloroform, ether, hexanes, ethyl acetate, THF, alcohol etc then it's probably fat soluble. (e.g. THC, amphetamine freebase, cocaine freebase, ethanol/chloroform, propofol, diazepam)
If it's water/DMSO/DMF soluble then it's probably well-adsorbed and excreted (amphetamine salts, water soluble benzos, GHB)
If it's insoluble in both then you won't adsorb it (chalk, sand etc)
 
Thanks sekio, but I have another question now.
For example - Hydroxyzine Pamoate - is not water soluble, not methanol soluble, but "freely" soluble in DMF. Does this drug change into a water soluble form in the stomach (perhaps through a reaction with Hydrochloric Acid) before it becomes effective then?
 
I imagine anything ionic is soluble under some conditions, even the outlandish ones (e.g. hassium tetroxide)

I think if you wash some vistaril with HCl you'll get hydroxizine hydrochloride. I could be wrong.

Why do all wikipedia chem and pharm articles now look like this?
 
235360287471352662 said:
I think if you wash some vistaril with HCl you'll get hydroxizine hydrochloride. I could be wrong.
Click to expand...
No Sir, you are right: Treating hydroxyzine (sufficiently long) with HCl will result in the hydrochloride salt. The pamoate is intentionally used because of the mentioned low solubility, due to which it releases the active drug comparatively slow. Hence, it acts as kinda sustained release form of the drug.
I think that this description at Wiki is wrong:
In pharmacology, the salt form of pamoic acid (pamoate ion) can be used as a counter ion of a drug compound to increase the solubility of the drug in water. The presence of multiple oxygen atoms enables significant hydrogen bonding to occur. Hydrogen bonds facilitate the dissolution of compounds in water.
Click to expand...
 
That makes sense because it lasted a long time in my system, i.e. made me hyper w/insomnia for almost 3 days. It is also sold as the Hcl salt as brand name atarax so essentially vistaril turns into atarax in your stomach. You damn BLers are so smart! You guys should be doctors. My doctors would never know that kind of info.
 
^ Are you saying you experienced insomnia from hydroxyzine? That would be a bit of an atypical reaction.
 
^It happens. It is indicated that it happens more often in children and the elderly so maybe I'm just an elderly child or something! I've heard from several people that promethiazine and hydroxyzine make them go crazy. Pharmocologically it makes no sense, so I really wonder what goes on to make a "sedating" antihistamine so damn meth-like? I also had sedating reactions to hydroxyzine prior to getting amped up the last time to add to the confusion.

I often get stimulated these days from opiates, valerian, and it happened with benzos too. I wish coffee would make me sleepy to balance this out but it doesn't! Anybody got explainations to the mechanisms of paradoxical stimulation?
 
Well I don't know what common drugs are totally water and fat insoluble, but possible mechanisms would be if there is a receptor on the inner lining of the stomach or gut to internalize the molecule or to simply take a large enough dose that it forces itself through a site of administration (think injection for this one). Else it probably isn't even processed, it is simply excreted by passing through the digestive tract. Just remember the stomach produces HCl (pH 2-3) during digestion so there really isn't that much that won't be solubilized (and uptaken or degraded) to some extent.

Also consider that many drug solubility studies will be summarized outside of the original work or paper to contain the primary points. So one person might read a paper about methamphetamine solubility and say this is not water soluble. Well the fact is, it is water soluble, just barely and probably such a little number that it is very hard to measure in the lab. A publication might list water solubility as < 0.001 mg/mL or ND as not determined, but that doesn't mean that some very small amount cannot get in.
 
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Just to jump in and sort of ask a related question::

Based on what we think we know about ivory wave/bath salts/etc;; if an amount of that powder were to get lodged behind your teeth SHOULD it dissolve in your saliva or would it gel up?
 
LOL! What do we actually know about those ridiculous "bath salts"? Next to nothing, I'd say. Neither are the active agents always the same, nor are the auxiliary ingredients.
 
I am having some very unpleasant side effects from Letrozole. My Oncologist took me off of it for two weeks and my symptoms have not improved. I began thinking about solubility. It is freely soluble in dichloromethane, slightly soluble in ethanol and not in water. So, my question to you smart people is: is this thing fat soluble and am I not clearing it because I have extra body fat? If so, maybe I just need to be off of it for a while longer? I would appreciate any light you may be able to shed on this. Thanks.
 
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