Pharmacokinetics
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Pharmacokinetics is the effect that the body has on drugs.
All aspects of pharmacokinetics can be covered by the acronym ADME, which stands for:
Absorption
Distribution
Metabolism
Excretion
These underpin how a clinician chooses to use a drug and a good knowledge of a drug's pharmacokinetics will help one predict when therapeutic failure may occur and to enable one to safely use unliscensed products or multiple drugs on one patient. It must also be remembered that the the follwing factors also have an effect on a drug's pharmacokinetics:
- renal, hepatic and gastrointestinal disease
- multiple drug therapy
- species treated
- age
- drug formulation
Absorption
Drugs are most usually small molecules (<1000 molecular weight) and thus can pass through cell membranes through passive diffusion and facilitated transport. For further information on these processes please look here. To cross vascular endothelium drugs usually are able to squeeze through the gaps between the cells. The size of these gaps varies between different locations in the bosy; in the liver the gaps ate large but in the central nervous system these gaps are tight junctions.
The ability of a drug to cross the phospholipid bilayer not only infuences the rate and extent of its absorption but also the rate and extent of it's distribution, metabolism and elimination.
Below are the main factors affecting absorption:
Properties of the Drug
- Lipid solubility - the more lipid soluble a drug the easier it is absorbed across the bilayer
- Chemical nature - ie. Is it basic or acidic? Is it ionised or not?
- Molecular weight
- Stability in the gastro-intestinal tract - only applies to orally administered drugs
Physiological Variables
- pH at site of absorption
Many drugs are either a weak base or a weak acid and so will exist in both an unionised and ionised form in the same solution. The ratio of the two forms is dependent upon the pH of the location of the drug.
The ionisation reaction of a weak acid is
AH =Ka A- + H+
and its dissociation constant pKa is given by the Henderson-Hasselbach equation:
pKa = pH + log10 ([AH]/[A-])
The ionisation reaction of a weak base is
BH+ =Ka B + H+
and its dissociation constant pKa is given by the Henderson-Hasselbach equation:
pKa = pH + log10 ([BH+]/[B])