Drug passage across cell membrane

Methods of crossing the cell membrane

• Passive diffusion
  * Non-ionised drugs
• Facilitated diffusion
  * e.g. steroid and amino acid absorption from the gut
• Active transport
  * e.g. Na/K ATPase
  * Can be primary active transport, or secondary active transport (co-transport or antiport)
• Pinocytosis

Factors influencing diffusion rate

• Molecular size
  * Graham's law = diffusion rate is inversely proportional to the square root of the MW
• Concentration gradient
  * Fick's law = diffusion rate is proportional to the concentration gradient
  * Bowman's principle = Use of less potent drugs requires larger doses, which actually increases concentration gradient and hasten onset of action
• Ionisation
  * Low ionisation increases diffusion rate
  * Weak bases at high pH and weak acids at low pH are non-ionised, thus faster diffusion rate
• Lipid solubility
  * High lipid solubility increases diffusion rate
• Protein binding
  * Only unbound fraction of the drug is available for diffusion