Most drugs are bound to proteins when they circulate in the body. This makes sense when considering the general solubility rules of chemistry. If a drug is very simple chemically, e.g., an elemental salt such as lithium, it will easily dissolve into the aqueous environment of the blood and widely distribute through the circulation. However most drugs are not that simple, they are usually complex organic molecules with variable solubility in water.
For drugs that are not highly soluble in an aqueous environment, some carrier protein will be needed to solubilize that drug into the blood. Serum contains a myriad of proteins. Although these proteins themselves are water soluble (since they are found dissolved in blood), they often contain lipophilic regions on them, which can bind non-polar drugs and thus carry these drugs through the circulation.
Key points concerning drug-binding proteins:
- Albumin is the major drug-binding protein in serum.
- Albumin is an alkaline protein, so acidic and neutral drugs primarily bind to it.
- If albumin binding sites become saturated, acidic and neutral drugs can bind to lipoproteins.
- Alkaline drugs tend to bind to globulins, particularly to a globulin called alpha-1 acid glycoprotein.
- Only free, unbound drugs are able to bind drug receptors on cells and have therapeutic effects.
An equilibrium will exist in the body between free and protein-bound drugs and between free and receptor-bound drugs.
