Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either weak acids or bases. The ionized forms of these drugs cannot dissolve in lipids and cannot cross the cell membrane. However, the nonionized forms that can dissolve in lipids can diffuse readily.

The distribution of a drug across a cell membrane depends on two factors: the drug's pK_a and the pH gradient across the membrane. pK_a refers to the acidity constant of the drug, while pH measures the acidity or alkalinity of the environment. Consider an example of a weakly acidic drug in stomach gastric juice. In the stomach, where the pH is lower than the drug's pK_a, the drug remains primarily undissociated and can easily diffuse across the barrier. The drug dissociates readily once in the plasma, where the pH is higher than the drug's pK_a. Because the ionized form of the drug cannot diffuse back through the barrier, this form is primarily found in the plasma.