In the context of weak acids, what effect does longer gastric residence time have on absorption?

• A. Decreases absorption
• B. No effect
• C. Increases absorption
• D. Only affects solubility

Answer: (C)

Longer gastric residence time increases absorption for weak acids because the stomach’s acidic environment keeps the drug largely in its non-ionized form, which crosses membranes more readily. When the drug stays in the stomach longer, more of it can be absorbed before it moves to the higher-pH intestine where it becomes more ionized and less permeable. This effect relies on the drug having enough solubility and dissolution to be present in gastric fluid; if dissolution is rate-limiting, the benefit may be limited. In short, extending gastric residence time provides a longer window for the unionized fraction to permeate the gastric mucosa, boosting overall absorption.