The Nature of Drug-Protein Interaction

Blood is the system by which a drug is transported from the site of administration to the site of action. The drug is either in solution in the water of the plasma or is bound to the blood proteins. Among the proteins, the serum albumins can carry many types of drugs, but hemoglobins, lipoproteins, and certain globulins are also important. It is customary to refer to the phenomenon of drug uptake in the blood as blood solubility. The phenomenon is visualized by many as a classical “solution” which involves the formation of a homogenous mixture of the drug with the blood components. As a result, classical physical chemistry of solutions is used to describe diffusion gradients for the movement of drugs into and out of the blood. The use of the phrase “blood solubility” is an unfortunate one, for often the drug is transported mainly as a complex with protein. For example, xenon, a gaseous anesthetic, is not very soluble in water and up to 50% is carried by the blood proteins (principally hemoglobin). Thiopental, a very fast acting drug, is 65% bound to albumin and phenylbutazone can be 95% bound.