How does PH change drug absorption?

[scilearner]

Hello,

It is long time since I have learned chemistry.

 

My book says many drugs are strong acids or weak bases. Furthermore a strong acid in an acidic media is more lipid soluble and can cross cell membrane. This I can understand.

 

HA <---> A- + H+

 

So with a strong acid HA is lower and A- is higher at equilibrium. If I suddenly increase H+ ions, then HA would further increase which is more lipid soluble and cross cell membrane. Now the book says weak bases are ionised and more soluble in acidic media. Ok if I use the same reaction for that,

 

HA <---> A- + H+

 

So with a weak base HA is higher and H+ is lower. Then if I suddenly increase H+ ions, then HA would further increase, so it must be lipid soluble rather than ionic in acidic media. I think I'm doing something wrong with the 2nd reaction. Do I have to use OH instead along with water equation for this one, then it makes more sense

 

HA <----> A- + OH-

 

The thing is I'm thinking weak base is something that produces less H+ ions, is this wrong is weak base something that produces less 0H- ions.

 

Thank you

Edited October 30, 2011 by scilearner

[John Cuthber]

Meet my friend B

He's a base. He's also quite lipophilic.

If there are lots of protons about, he pairs up with one to form BH+

BH+ isn't lipophilic at all.

 

In acid conditions the absorption of basic drugs is slower.

[horsebox]

Don't have time to read your post but I'll answer the question in the title. When you ingest a drug orally it goes into your gastrointestinal tract. Unless the drugs target is in the GI tract, the drug needs to get absorbed into the blood stream. If you ingest a basic drug such as amphetamine then it will be protonated in the stomach because the pH in the stomach is pretty low. In other words the amphetamine gets converted into amphetamine hydrochloride by your stomach acid. Charged compounds (such as the amphetamine salt) generally don't bypass lipid membranes easily. Consequently, amphetamine hydrochloride will be much less likely to get absorbed through the stomach than amphetamine free base. This is why drug users report that taking antacids before ingesting the drug makes it more potent. Conversely if you ingest an acidic drug like GHB then low pH in the stomach means more of the drug gets absorbed because low pH will keep the GHB protonated. Taking an antacid in this case would mean more of the GHB gets converted into a salt and therefore less of it gets absorbed.

 

To sum it up: salts are far more polar than uncharged compounds and therefore they don't mix well with lipids. Since membranes are made of lipids, polar compounds like salts can't bypass membranes easily. If a drug has a basic or acidic group then the pH will determine whether the drug is charged or not.