Distribution - Pharmacokinetics

Distribution

·        Drug can be bound or unbound in both plasma and tissues

·        Drugs bind to albumin (acidic drugs), a1 acid glycoprotein (basic drugs), tissue proteins

·        Lipid solubility:

o   Penetrate lipid membranes easily (e.g. placenta, blood/brain barrier) 

o   Rapidly distributed, dissolves in fat ® plasma levels fall quickly, and large volume of distribution 

o   Is non-polar or unionised

·        Water soluble:

o   Excreted by kidneys (some also metabolised by liver)

o   Redistributes in water, smaller volume of distribution

·        Ionisation of acid or base:

o   Depends on pH and pKa (the pH at which 50% of drug is ionised) 

o   As pH ­ (becomes more alkaline) an acid becomes more ionised, and a base less ionised

o   Only unionised drug will diffuse across lipid membrane