Effects of Hydrophilic and Lipophilic Tendencies on the Biological Properties of Drugs


The characteristics conferred by predominant hydrophilic or lipophilic properties. Most drugs need both properties: lipophilic to cross membranes; hydrophilic to enable transport in and distribution by body fluids.


Predominantly lipophilic

  • Good membrane penetration
  • Good absorption after oral administration
  • Distributed in body fat
  • Cross blood–brain barrier
  • Hepatic metabolism
  • Longer half-life
  • First-pass effect possible
  • Clearance dependent on liver function and release from fat storage sites
  • Biliary excretion of hydrophilic metabolites (molecular weight 400 Dalton)
  • Possible interaction with other hepatically metabolized drugs


Predominantly hydrophilic

  • Poor membrane penetration
  • Poor absorption after oral administration
  • Distributed in body water
  • Does not cross blood–brain barrier
  • Cleared renally unchanged
  • Shorter half-life
  • Clearance dependent on renal function
  • Increased plasma protein binding
  • Possible interaction with other protein-bound drugs


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