Protein Binding

Definition and properties

When active pharmaceutical ingredients enter the bloodstream, they often bind to proteins, especially albumin, to a greater or lesser extent. This phenomenon is called protein binding, and it is reversible: drug + protein ⇌ drug-protein complex Protein binding is important, first, because only the free portion distributes to tissues and induces a therapeutic effect. The bound and unbound portions are in equilibrium. If the plasma concentration drops, the bound drug is released from its depot by the binding sites on the proteins. Protein binding thus also protects the drug from elimination and prolongs its half-life. Second, different drugs can compete for the binding sites on the proteins. This can result in drug-drug interactions, because the active ingredient with the higher affinity for the protein can displace the other active ingredient, increasing its free concentration and thus also increasing its effects or adverse effects. For example, both the anticoagulant phenprocoumon (Marcoumar) and the analgesic ibuprofen (e.g., Algifor) have a high protein binding of 99%. Only 1% is present in the pharmacologically active form. If even 1% is displaced from protein binding, the concentration of free drug doubles. Third, certain diseases can decrease protein binding and also thus increase the active drug concentration.