Most drugs are bound to proteins when they circulate in the body.

• Albumin is a 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 the globulin, alpha-1 acid glycoprotein.
• Only free, unbound drugs are able to bind drug receptors and have therapeutic effects.

An equilibrium exists in the systemic circulation between a free and protein-bound drug and between a free and receptor-bound drug. This is illustrated in the image to the right.