Most drugs penetrate biological membranes primarily through which process?

Most drugs penetrate biological membranes primarily through passive diffusion, which is a process driven by the concentration gradient of substances. In passive diffusion, molecules move from an area of higher concentration to an area of lower concentration without requiring energy input. This mechanism is essential for drug absorption, as most drugs need to cross cell membranes to exert their therapeutic effects.

Passive diffusion occurs because the lipid bilayer of cell membranes is relatively permeable to small, non-polar molecules, allowing them to traverse the membrane easily. Factors such as the drug's molecular size, lipid solubility, and the presence of ionized versus non-ionized forms (which impacts solubility in the lipid membrane) all play significant roles in determining how effectively a drug can undergo passive diffusion.

In contrast to passive diffusion, processes like active transport and facilitated diffusion involve specific transport proteins and can require energy (in the case of active transport) or utilize gradients (in facilitated diffusion), making them less common pathways for the majority of drugs that penetrate membranes.