Kinetics of Protein Binding

Kinetics of Protein Binding describes drug–protein association and dissociation rates impacting pharmacokinetics and dynamics.

• Protein binding kinetics describes the interaction between a drug (D) and a protein (P) to form a drug-protein complex (DP).
• This process follows a reversible equilibrium:
• $D + P \;\rightleftharpoons\; DP$

Rate of Drug-Protein Binding

• The association and dissociation of drug-protein binding follow the rate equation:
• $k_{\text{on}}[D][P] = k_{\text{off}}[DP]$

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Equilibrium Dissociation Constant (K_D)

• At equilibrium, the dissociation constant is given by:
• $K_D = \frac{k_{\text{off}}}{k_{\text{on}}} = \frac{[D][P]}{[DP]}$
• A lower ​ indicates stronger drug-protein binding.
• A higher suggests weaker

Fraction of Bound and Unbound Drug

Bound Drug Fraction (fbound)

• • The fraction of the drug that is bound to the protein is:
  • $f_{\text{bound}} = \frac{[DP]}{[D_{\text{total}}]}$
  • where:
  • $[D_{\text{total}}] = [D] + [DP]$
    • (i.e., the total drug concentration is the sum of free and bound drug concentrations).

Unbound Drug Fraction (funbound)

• • The fraction of the drug that remains unbound is:
  • $f_{\text{unbound}} = \frac{[D]}{[D_{\text{total}}]}$
  • Since the total drug must be either free or bound:
  • $f_{\text{bound}} + f_{\text{unbound}} = 1$

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