Passive Absorption of Quinine in Stomach vs Ileum

[casio1990]

Homework Statement

The antimalarial drug quinine has pk_a = 8.4; is it likely to be absorbed by passive diffusion through lipid membranes in the stomach (ph = 0.9) or ileum (ph $$\approx$$ 8)? Why?

Homework Equations

n/a

The Attempt at a Solution

If the pH of the environment is equal to the pKa of the substance, then the substance will be ionized by 50%. Beyond that, I am unsure what the effect will be if the pH environment differs from that of the pKa. Strictly looking at the question from a chemistry viewpoint, I think that passive diffusion of quinine will more likely be absorbed in the ileum since the pKa and pH are close. On the other hand, I think that's a too large of an assumption to make since the differences between 8.4 and 8 are considerable. Biologically speaking, it would make more sense that passive diffusion of quinine should occur more readily at the ileum since the intestines are able to facilitate absorption better than in the stomach. While some absorption does takes place in the stomach, I don't think it compares to the intestines.

 

[silentelysium]

Hi casio1990,

I think you should revert back to the Henderson-Hasselbach equation to solve this one. The equation can tell you the percentage of non-ionised to ionised forms of the drug in the medium. However, you need to know if it is an acidic drug or a basic drug to calculate the percentages.

I think that quinine is as base so if the pH of the medium is bigger than the pKa of the drug then there will be more of the non-ionised form than the ionised form. If the pH of the medium is smaller than the drug then the ionised form of the drug dominates and less of the drug is absorbed.

Moreover, remember that passive diffusion is dependent accordingly to the factors of Fick's Law and the relative hydrophobocity of the drug. Also, the drug can only traverse through the epithelial cells in the gut when it is non-ionised. Diffusion cannot take place if the drug is ionised because it is unable to penetrate the cell wall. In the case of quinine above, it is more likely for it to be absorbed in the ileum than the stomach because when it is in the stomach it will protonate and be ionised.

"Strictly looking at the question from a chemistry viewpoint, I think that passive diffusion of quinine will more likely be absorbed in the ileum since the pKa and pH are close."

I don't think so. There are some drugs where there only a small difference in pH and pKa but there are large changes in their form composition in the medium.

"Biologically speaking, it would make more sense that passive diffusion of quinine should occur more readily at the ileum since the intestines are able to facilitate absorption better than in the stomach. While some absorption does takes place in the stomach, I don't think it compares to the intestines."

True, but remember some drugs are highly acidic like acetylsalicylic acid (aspirin). More of it is absorbed in the stomach than in the intestine. It is important for you to consider the pH and pKa factors in absorption also.

~silentelysium

 

[casio1990]

Thanks for your help!

Your hints gave me a better understanding of the question.