Biological Barriers to Drug Absorption

Study Notes

Drug absorption involves multiple steps from ingestion to reaching target cells
The body has various barriers (epithelia and endothelia) that influence drug absorption
Different types of epithelia and endothelia have varying permeabilities, impacting how easily a drug can pass through
Simple squamous epithelium, like blood vessel linings, demonstrates excellent permeability
Simple columnar epithelium, found in the stomach and intestines, exhibits very good permeability
Stratified squamous non-keratinized epithelium in areas like the vagina and cornea has intermediate to very good permeability
Stratified squamous keratinized epithelium, such as the skin, has poor permeability
The absorption site thickness plays a key role; absorption sites are often single-layered.
Regions needing strong barrier properties typically have multiple cell layers
Capillaries, which carry drug molecules, exhibit varying permeability across different tissues
Skin and muscle capillaries feature continuous endothelia with tight junctions, contributing to low permeability
Capillaries in the intestines have sinusoidal endothelia with open fenestrae, enabling high permeability
Liver capillaries boast fenestrated endothelia for substantial permeability

Transcellular route: Drugs permeate the phospholipid bilayer, favoring higher lipid solubility and low molecular weight
Paracellular route: Drugs pass through tight junctions between cells, influenced by tight junction permeability
Transporters: Key proteins aiding drug absorption and influencing drug concentration
Efflux transporters act to remove drugs, working against concentration gradients. P-Glycoprotein (P-gp) is a prominent example
Influx transporters often assist related molecules, such as nutrients
Some drugs can have similar structures to natural substrate molecules, improving their absorption.

Uniport: Transports a single substance
Symport: Transports multiple substances in the same direction
Antiport: Transports substances in opposite directions.
Active transport: Uses cellular energy, often against a concentration gradient
Examples of active transporters are Na+/K+ ATPase, which facilitates essential cell processes
Multiple families of transporters exist contributing to absorption of nutrients
PEPT1 plays a crucial role in transporting di- and tri-peptides in the intestines

Pinocytosis: Cells engulf small fluid droplets using membrane vesicles.
Receptor-mediated endocytosis: Cells take up specific substances using receptor ligands on cell surfaces, followed by vesicle formation and internalization.
Phagocytosis involves engulfing larger particulate material through membrane deformation

Optimal log P values are important for efficient drug absorption in various locations like the cornea, nose, lungs, etc.
Blood flow greatly affects drug distribution and absorption rates