Protein binding refers to the reversible association of a molecule, typically a drug or other bioactive compound, with one or more proteins in the body. T
The most common proteins involved in this process are plasma proteins, such as albumin, α1-acid glycoprotein, and lipoproteins.
Protein binding can significantly impact the pharmacokinetics and pharmacodynamics of a drug, influencing its distribution, metabolism, and elimination.
Types of Protein Binding
Albumin binding
α1-Acid glycoprotein binding
Lipoprotein binding
Mechanism of Protein Binding
Hydrophobic Interactions: Lipophilic drugs associate with hydrophobic regions in protein structures.
Electrostatic Interactions: Oppositely charged groups on the drug and protein attract each other.
Hydrogen Bonding: A hydrogen atom covalently bonded to an electronegative atom interacts with another electronegative atom in the protein.
Van der Waals Forces: Weak attractive forces between molecules result from induced or instantaneous dipoles.
Binding Sites
Specific Binding: Occurs at designated sites on the protein (e.g., hormone receptors).
Non-Specific Binding: Involves multiple weak interactions across the protein surface.
Factors Affecting Protein Binding
Drug Concentration: High drug concentrations can saturate binding sites.
Affinity: High-affinity drugs bind more tightly to proteins.
Competition: Different drugs can compete for the same binding sites.
Physiological Conditions: pH, temperature, and the presence of other molecules can influence binding.
Implications of Protein Binding
Free vs. Bound Drug: Only the unbound (free) fraction is pharmacologically active.
Distribution: Protein-bound drugs are typically confined to the vascular compartment.
Elimination: Bound drugs are usually not readily filtered by the kidneys.
Drug Interactions: Competition for binding sites can alter drug efficacy and toxicity.
Measurement of Protein Binding
Equilibrium Dialysis: Separates free and bound drug across a dialysis membrane.
Ultrafiltration: Uses centrifugal force to separate free drug from protein-bound drug.
Chromatographic Methods: HPLC can quantify free and bound drug fractions.