3.2:
Drug Absorption Mechanism: Passive Membrane Transport
In drug absorption via passive transport, small lipid-soluble drugs traverse by diffusion across the cell membrane down the concentration gradient.
The rate of transfer is directly proportional to the drug's lipid–water partition coefficient. The greater the partition coefficient, the more lipid-soluble is the drug, and the more rapid is its diffusion.
Most drugs are weak acids or weak bases. The lipid-insoluble ionized species do not permeate the membrane, while the lipid-soluble nonionized forms diffuse readily.
The transmembrane distribution of a drug depends on the pKa of the drug and the pH gradient across the membrane.
For instance, consider a weakly acidic drug dissolving in the gastric juice of the stomach.
In the gastric compartment, the drug remains primarily undissociated because its pKa is higher than the pH, and this form diffuses easily across the barrier.
In the plasma, where the drug's pKa is lower than the pH, the drug readily dissociates. Furthermore, because the ionized form of the drug cannot diffuse through the barrier, this form predominates in the plasma.
3.2:
Drug Absorption Mechanism: Passive Membrane Transport
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 pKa and the pH gradient across the membrane. pKa 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 pKa, 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 pKa. Because the ionized form of the drug cannot diffuse back through the barrier, this form is primarily found in the plasma.