In most cases, drugs move through the cellular membrane via passive diffusion down its concentration gradient. This transport does not require any expenditure of energy. Passive transport depends on the structure of the drug as the membrane is semipermeable. In particular, drugs that possess some nonpolar groups can penetrate cellular membranes while polar molecules enter cells via channels or protein carriers (facilitated diffusion). Nonionized drugs cross the membrane proportionally to their lipid-water partition coefficient while the transport of weak electrolytes depends also on pH.
Some drugs cross the membrane via active transport. Primary active transport is directly associated with the use of ATP while secondary active transport is linked to the formation of a gradient of certain molecules or ions (i.e., Na+/K+). Symporter transports drugs and a specific ion in the same direction while antiport moves them in the opposite direction. Finally, some drugs can penetrate the cell via pinocytosis or endocytosis - invaginations of membranes with the formation of vesicles.