Drug absorption and distribution

Drug absorption and distribution

1. movement of drug molecules across cell barriers

   • small molecules
     • diffusion through lipid
       • non-polar molecules able to penetrate membrane easily
       • permeability coefficient (P)
         • factors affecting P
           • Solubility
             • expressed as partition coefficient
           • Diffusivity
             • expressed as diffusion coefficient
     • carrier-mediated transport
       • Solute carrier (SLC) transporters
         • organic cation transports (OCTs)
         • organic anion transporters (OATs)
         • coupled to electrochemical gradient of Na+ across membrane
           • transport can occur against electrochemical gradient
             • Antiport - exchange of one molecule for another
             • symport - transport 2 molecules together in same direction
       • ATP-binding cassette (ABC) transporters
         • active pumps fuelled by ATP
       • P-glycoprotein

2. Absorption

   • movement of drug into systemic circulation
   • Factors affecting absorption
     • stomach acidity
     • physiochemical
     • presence of food in stomach/intestines
     • Routes of administration
       • oral (PO)
       • intravenous (IV)
       • intramuscular (IM)
       • Transdermal
       • subcutaneous
     • lipid solubility
     • blood flow

3. Administration main routes

   • Oral
     • some non-polar drugs applied to buccal mucosa are directly absorbed from oral cavity
     • passive transfer rates determined by ionisation and lipid solubility
   • Sublingual
     • absorption directly from oral cavity to systemic circulation w/o entering portal system
   • Rectal
     • used for drugs requiring local/systemic effects
   • Application to epithelial surfaces
     • nasal sprays and eye drops
   • Administration by inhalation
     • use for volatile and gaseous anaesthetics
   • Administration by injection
     • subcunatenous
     • intramuscular
     • intravenous
     • intrathecal
     • intravitreal