The efficacy of certain drugs is affected by pH. Many drugs are absorbed into the blood through cells lining the stomach or the small intestine by direct diffusion across the plasma membrane. Since the interior of the plasma membrane is hydrophobic, uncharged molecules cross the membrane faster than charged (ionized) molecules. If a drug contains an ionizable group, its absorption will be dependent on the pH. Let us now apply your understanding of acid/base chemistry and solubility to explain the pH dependence of codeine absorption. Codeine, shown below in its uncharged form, is an opiate drug used for pain and cough relief. The pKa of codeine is 8.2.

Question

The efficacy of certain drugs is affected by pH. Many drugs are absorbed into the blood through cells lining the stomach or the small intestine by direct diffusion across the plasma membrane. Since the interior of the plasma membrane is hydrophobic, uncharged molecules cross the membrane faster than charged (ionized) molecules. If a drug contains an ionizable group, its absorption will be dependent on the pH. Let us now apply your understanding of acid/base chemistry and solubility to explain the pH dependence of codeine absorption. Codeine, shown below in its uncharged form, is an opiate drug used for pain and cough relief. The pKa of codeine is 8.2.
￼￼
a. In the structure above, is codeine depicted in the HA or A- form?

b. On the diagram above, draw the charged form of codeine.

c. The pH in the stomach is approximately 2.0 and in the intestine approximately 8. Calculate what proportion of codeine will be in its neutral form in the stomach and in the intestine (as ratio of neutral to charged species). Fill in the table below with your answers, and show your work.

neutral/charged codeine
￼
stomach
￼
￼
intestine
￼
d. Is codeine absorbed more efficiently in the stomach or in the intestine?