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Help! pKa & absorption

Thread: Help! pKa & absorption

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  1. tbd_guy said:

    Help! pKa & absorption

    A question on a pharm test I recently took goes as follows:

    An 85-year old man was recently admitted to a nursing facility. Medications taken orally by the patient include:

    - Sertraline (base, pka = 9.5)
    - Diazepam (base, pka = 3.0)
    - Amiodarone (base, pka = 7.4)

    - Theophylline (acid, pka = 8.8)
    - Ibuprofen (acid, pka = 4.8)

    Shortly after administration, which of the following drugs was most likely concentrated inside the gastric cells?
    The professor then clarified that the question is meaning to ask which drug best crosses the stomach and enters the blood.

    My understanding is that all the bases will be protonated and ionized at the gastric pH of 1.5 and thus unable to be absorbed. This leaves the acids. By the Henderson-Hasselbach equation, the acid with the pka higher and further from the pH will have more drug in protonated (unionized) form. This would be Theophylline. The answer, however, is Ibuprofen.

    The profs reasoning is something along the lines of Ibuprofen's pKa being closer to the pH of the solution and thus more of it being unionized and able to cross the stomach. I'm having a hard time making sense of this... what am I missing?

    Thank you!!
  2. rologist said:
    Some report that average gastric pH is more like 2.5-3, with a range of 1.5-3.5. But yes, your reasoning is correct, and theophylline is the most correct answer, since the pKa minus pH value is greater than that of ibuprofen. Remember it is not 100% unionized to ionized, but a proportion of unionized to ionized, and with a pKa of 8.8, there will be a greater proportion of -COOH groups unionized than ionized for theophylline than for ibuprofen in gastric juice. Both will be significantly concentrated in the gastric mucosal cells, but theophylline moreso. And I think the professor's clarification is needless. It doesn't help. Either the drug is absorbed through biomembrane favorably or it is not. You can think of weak bases as having -NH4+ groups, which are overwhelmingly ionized at gastric pH. and therefore not significantly absorbed. Nearly all pharmaceuticals are labelled as weak acids or weak bases.
    Last edited by rologist; 10-27-2015 at 03:29 PM.
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