The process of oral drug absorption can be influenced by several factors. Weakly acidic drugs tend to be absorbed more readily from the stomach due to their nonionized state. However, absorption may be less efficient in the upper intestine, where drugs are often ionized. Interestingly, despite the stomach's apparent advantage for drug absorption, its mucous layer can hinder diffusion. Its surface area is also smaller than the intestine's, which can further slow down the absorption rate.

In contrast, the intestinal villi offer a much larger surface area for absorption, which, combined with high blood flow, makes the intestine a prime site for drug absorption. Furthermore, food in the stomach can interfere with absorption, where drugs can form complexes with food constituents. Additionally, food can delay gastric emptying, or the movement of drugs into the small intestine, further slowing down absorption. Certain physiological conditions, such as diarrhea, can also impact drug absorption by accelerating the movement of gut contents. Lastly, the gut epithelium, which contains P-glycoprotein transporters, can pump drugs back into the gut lumen, reducing their absorption into the blood.