biological barriers to drug absorption

• What type of epithelium has excellent permeability?

  Simple squamous epithelium
• Where is simple squamous epithelium located?

  Lining blood vessels and alveoli
• What is the permeability of stratified squamous keratinised epithelium?

  Poor
• What is the role of capillary endothelia in drug absorption?

  They allow drug penetration into tissues
• What is the pore size of continuous capillaries?

  5 nm
• What type of capillaries have open fenestrae?

  Hepatic capillaries
• What is the permeability of capillaries in the brain?

  Tight junctions (<1 nm)
• What must a drug do to reach the target cell?

  Be absorbed across epithelia or endothelia
• What are the routes of epithelial transport for drugs?

  • Paracellular diffusion
  • Carrier mediated endocytosis
  • Passive & carrier mediated transport
  • Endocytosis
• What is favored for passive diffusion across epithelial membranes?

  Higher lipid solubility
• What does the variable $k$ represent in drug transport?


  $k =$$D \times A \times h$
• What is the optimal log P for nasal absorption?

  1 to 4
• What is the role of drug transporters?

  Move drug molecules across membranes
• What are the types of transport modalities for drug transporters?

  • Uniports: Move one substrate
  • Symports: Move two substrates together
  • Antiports: Move substrates in opposite directions
  • Active transporters: Require energy
• How many transporter families are in the solute carrier gene series?

  40 transporter families
• What is the function of PEPT1?

  Active transport of di- and tri-peptides
• What is pinocytosis?

  Engulfment of small droplets of fluid
• What triggers receptor-mediated endocytosis?

  Receptor-ligand interactions
• What is the size of particles involved in phagocytosis?

  Larger than 500 nm
• What factors control paracellular permeability?

  • Differences in tight junctions
  • Paracellular permeability
  • TEER (trans-epithelial electrical resistance)
• What does a lower TEER indicate?

  Higher permeability
• What is the optimal flux for the cornea?

  1102 for <500 Da
• What is the role of tight junctions?

  Maintain polarity and barrier function
• What are the examples of drug transport routes?

  • Transcellular: Passive diffusion
  • Carrier mediated: Captopril, Cefalexin
  • Paracellular: Passive diffusion
• How does blood flow affect drug absorption?

  Poor perfusion reduces absorption rate
• What is the flow rate for well perfused viscera?

  50-400 mL/min/100g
• What do efflux pumps do?

  Pump drugs out of cells actively
• What is P-glycoprotein?

  A common drug efflux pump
• How does grapefruit juice affect drug absorption?

  Inhibits P-glycoprotein activity
• What are the routes of drug absorption?

  • Intravenous: Capillaries in target tissue
  • Intramuscular: Capillaries in muscle
  • Sublingual: Sublingual mucosae
  • Oral: Mucosa of small intestine
  • Rectal: Rectal mucosa
• What is the focus of biopharmaceutics in this context?

  Physicochemical properties influencing absorption