Protein Binding
‘Protein binding often mentioned but generally poorly understood.’
Summary
- Drugs are either bound to something or are free: an equilibrium is maintained between these two states that is dependent upon the drug and the binding affinity and capacity
- Affinity refers to how much a drug ‘sticks’ to the receptor, and capacity refers to how many receptors there are
- Only free drug is active i.e. is available to bind to receptors, get metabolised or just get eliminated. The fraction of free drug is dependent upon affinity and capacity.
- While changes in protein binding are generally not very important in clinical medicine they can be in clinical toxicology.
- Generally for changes in protein binding to be significant the drug needs to be greater than 90% bound
- Protein binding interactions between drugs are rarely of clinical significance as the onset is normally so gradual that increases in free drug are dealt with by metabolic processes
- The major carriers are:
- Albumin
- Alpha 1 glycoprotein
- Circulating lipids
- The proteins have specific binding sites (individual proteins may have multiple sites) and as a consequence there is: * Competition for and Saturation of sites
- Genetic variation
- In addition the actual amount of carrier e.g. albumin may be important in determining how much can be carried. This can be important in disease states that alter the amount of circulating protein. Most commonly, disease states increase α1-acid glycoprotein concentration while reducing albumin concentration
- Most assay systems measure total drug i.e. bound plus free drug