Learning Objective
To understand the major factors that influence drug permeation across biological membranes, including solubility characteristics, concentration gradients, surface area, and tissue vascularity, and to apply these principles to predict drug absorption and biodisposition.
Drug permeation refers to the movement of drug molecules across biological membranes—a process essential for absorption, distribution, and overall biodisposition. Several key factors determine how efficiently a drug permeates:
Solubility
Lipid solubility is critical because most biological membranes are composed of lipid bilayers. Drugs with higher lipid solubility diffuse more rapidly through these membranes.
Concentration Gradient
Drugs move passively down their concentration gradient from areas of high concentration to low concentration. Importantly, only the free, unbound, and unionized fraction of a drug contributes to this gradient and is capable of crossing membranes efficiently. Ionized or protein-bound forms have limited permeability.
Surface Area and Vascularity
The greater the surface area available for absorption, the more efficiently a drug can permeate. Highly vascularized tissues enhance drug uptake by maintaining the concentration gradient and carrying the absorbed drug away rapidly. For example, the small intestine—with its large surface area and rich blood supply—supports highly efficient absorption.
