Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.

However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive transport permits drug molecules to move freely through the lipid bilayer along the concentration gradient without energy expenditure.

Active transport allows cells to move drugs against an electrochemical gradient. In primary active transport, membrane transporters utilize ATP to move drugs against the concentration gradient. Drugs are sometimes swapped for other solutes moving along their gradient via symport or antiport mechanisms. Such a process is called secondary active transport.

Lastly, vesicular transport is a method where the cell membrane invaginates to internalize large macromolecules or hydrophilic particles. This process encompasses phagocytosis (cell eating), the engulfment of large foreign particles or macromolecules, and pinocytosis (cell drinking), the internalization of fluids bearing small particles. These processes illustrate the complex and diverse ways drugs can navigate cellular barriers to reach their target sites.