For a weak acid, the higher the pH, the lower the ratio of un-ionized to ionized forms. When the weak acid is given orally, the concentration gradient for un-ionized drug between stomach and plasma tends to be large, favoring diffusion through the gastric mucosa. One theory is that a carrier component combines reversibly with the substrate molecule at the cell membrane exterior, and the carrier-substrate complex diffuses rapidly across the membrane, releasing the substrate at the interior surface. The process does not require energy expenditure, and transport against a concentration gradient does not occur. Substrates may accumulate intracellularly against a concentration gradient.
Active transport appears to be limited to drugs structurally similar to endogenous substances.
These drugs are usually absorbed from sites in the small intestine. Active transport processes have been identified for various ions, vitamins, sugars, and amino acids. Fluid or particles are engulfed by a cell. The cell membrane invaginates, encloses the fluid or particles, then fuses again, forming a vesicle that later detaches and moves to the cell interior. This mechanism also requires energy expenditure.