Drug absoption: Transcellular Transport

• For a drug to be absorbed after oral administration, it must pass through a biological barrier.

Mechanisms of Drug Absorption

• Three broad categories of drug transport mechanisms involved in absorption:
  • Transcellular/intracellular transport
  • Paracellular/intercellular transport
  • Vesicular transport

Transcellular/Intracellular Transport

• Passage of drugs across the GI epithelium.
• Most common pathway for drug transport.
• There are three steps
  • Permeation of GI epithelial cell membrane, a lipoidal barrier (major obstacle to drug absorption).
  • Movement across the intracellular space (cytosol).
  • Permeation of the lateral or basolateral membrane (secondary importance).
• Various transcellular transport processes involved in drug absorption:

Passive Transport Processes

• Do not require energy other than molecular motion (Brownian motion) to pass through the lipid bilayer.
• Types:
  • Passive diffusion
  • Pore transport
  • Ion-pair transport
  • Facilitated- or mediated-diffusion

Active Transport Processes

• Requires energy from ATP to move drug molecules from extracellular to intracellular milieu.
• Two types:
  • Primary active transport
  • Secondary active transport
    • Symport (co-transport)
    • Antiport (counter-transport)

Paracellular/Intercellular Transport

• Transport of drugs through the junctions between the GI epithelial cells.
• This pathway is of minor importance in drug absorption.
• Two paracellular transport mechanisms:
  • Permeation through tight junctions of epithelial cells
    • Occurs through openings slightly bigger than aqueous pores.
    • Insulin and cardiac glycosides are taken up by this mechanism.
  • Persorption
    • Permeation of drug through temporary openings formed by shedding of two neighboring epithelial cells into the lumen.
• Paracellular transport differs from pore transport:
  • Paracellular involves transfer of drug across epithelium and through cellular junctions.
  • Pore transport transfers molecules from outside of the epithelial cell into the cell through pores in the cell membrane.

Vesicular or Corpuscular Transport (Endocytosis)

• Similar to active transport, these are energy-dependent processes.
• Involves transport of substances within vesicles into a cell.
• Classified as transcellular because the mechanism involves transport across the cell membrane.
• Two categories:
  • Pinocytosis
  • Phagocytosis