Τόμος 4 (1986) – Τεύχος 4 – Άρθρο 2 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 4 (1986) – Issue 4 – Article 2 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

CH. T. PLESSAS AND A. BENAKIS

4: 157-188 (1986)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

4: 157-188 (1986)

The binding of drugs to proteins is an important pharmacokinetic para­meter and the model for drug-receptor interactions. Many methods are available for the study of drug protein binding phenomena and there are also many ways to interpret the binding data. Acidic (anionic) drugs bind largely to plasma albumin, while the basic (cationic) drugs associate with α₁-acid glycoprotein, lipoprotein, y-globulins and albumin. Although much em­phasis has been placed on the binding of drugs in the blood, binding also takes place in the tissues. In general, drug-protein interactions occur as a result of hydrophobic binding due initially to electrostatic attraction reinforced by hydrogen bonds and van der Waals forces; therefore such binding is generally reversible and serves as a carrier mechanism for the functionally active unbound drug. Additionally, the absorption, distribution and elimination (metabolism and excretion) may be limited by plasma binding. The extent of binding is depen­dent nest only on the concentration of the drug, but also the amount of macromolecule to which binding occurs and its affinity, and the pre­sence of competitive binding substances. Many physiological states (i.e. age, sex, genetics, pregnancy) and pathological conditions (i.e. cirrhosis, nephrotic syndrome, main nutrition. Kwaskiorkor, inflammatory diseases, stress, etc.) may induce changes in the plasma pro­teins and therefore variations in the binding of drugs. Displacement interactions involving plasma or tissue binding sites have been impli­cated as the causative mechanisms in many drug interactions; these displacement interac­tions do become important clinically namely when the displacing drug is administered quic­kly to the patient by the intravenous route, during therapeutic drug monitoring and in cer­tain drug disposition studies which involve the use of heparin lock for blood sampling.

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