Week 5 lecture 2

• What is the definition of partition coefficient ?

  a constant which is the ratio of concentration of compound in organic phase to the concentration in the aqueous phase at equilibrium
• what is the equation for partition coefficient?

  P= Corg/Caq
• what is the partition coefficient of an unionised drug called?


  true partition coefficient
• what does it mean if the Ptrue is greater than 1?

  Corg>Caq, so compound is hydrophobic/lipophilic
• what does it mean if Ptrue is less than 1?

  Corg<Caq, so compound is hydrophilic/lipophobic or polar
• what can the partition coefficient be used to predict?

  absorption, distribution and elimination of drugs within the body
• What can chemical polarity effect?

  solubility, intermolecular forces
• What is chemical polarity dependent on?

  the difference in electronegativity between atoms in a compound and the asymmetry of the chemical structure
• what are compounds that have the capacity to form hydrogen bonds with water considered as?

  hydrophilic or polar
• why is methane considered no–polar?

  Symmetry
• what do Hansch-Fujita parameters describe?

  the contribution of various functional groups to the liphophilicity of a compound
• what are the hydrophobic functional groups?

  aromatic hydrocarbons, aliphatic hydrocarbons, halogens
• are hydrophobic functional groups positive or negative pi?

  positive
• what does a predominance of +pi functional group cause in the partition coefficient?

  increase
• what does increasing the partition coefficient mean?

  the molecule is more lipid soluble, better able to pass through the lipid membranes
• what are the hydrophilic/polar functional groups?

  hydroxyl group, carboxyl group, amine, ether, amide
• What does a predominance of negative pi functional groups lead to in the partition coefficient?

  decrease
• what does a decrease in the partition coefficient mean?

  the molecule is less lipid soluble and less able to pass through the lipid membranes
• What can partition coefficient be used in combination with to predict the distribution of a drug compound in a biological system?

  pKa
• what factors are related to the log P value of a drug?

  absorption, excretion, penetration of CNS
• if the drug is a weak acid or weak base, what will considerable alter the partitioning of a compound?

  ionisation
• how much is the permeability of the unionised form of a drug more than the ionised form across a phospholipid membrane by passive diffusion?

  10 to the 8
• what assumption do we make in our approach?

  only the unionised drug will partition into the hydrophobic organic layer
• what does the % of unionised compound depend on?

  pKa of molecule and pH of solution
• for a neutral compound, is the partition coefficient the same at any pH value?

  yes
• for which molecules does the partition coefficient depend on the pH at which it is measured?

  Acidic and basic molecules
• what is it called when the partition coefficient depends on the pH at which is it measured?

  apparent partition coefficient
• what is P apparent also called sometimes?

  D or distribution coefficient
• what does the apparent partition coefficient depend on?

  the proportion of unionised form of the drug present in solution
• what is the equation for P apparent?


  P apparent = Ptrue x f unionised
• what is f unionised?


  the fraction of the total amount of drug unionised at a certain pH
• if the drug is totally unionised then is P apparent equal to P true?

  yes