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Related Concept Videos

Drug Distribution: Plasma Protein Binding01:29

Drug Distribution: Plasma Protein Binding

9.0K
Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
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The Integrated Rate Law: The Dependence of Concentration on Time02:39

The Integrated Rate Law: The Dependence of Concentration on Time

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While the differential rate law relates the rate and concentrations of reactants, a second form of rate law called the integrated rate law relates concentrations of reactants and time. Integrated rate laws can be used to determine the amount of reactant or product present after a period of time or to estimate the time required for a reaction to proceed to a certain extent. For example, an integrated rate law helps determine the length of time a radioactive material must be stored for its...
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Expected Value01:15

Expected Value

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The expected value is known as the "long-term" average or mean. This means that over the long term of experimenting over and over, you would expect this average. The expected average is represented by the symbol μ. It is calculated as follows:
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The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

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The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
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Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.6K
Factors Affecting Protein-Drug Binding: Protein-Related Factors01:20

Factors Affecting Protein-Drug Binding: Protein-Related Factors

575
Drug binding to proteins is a key aspect of pharmacokinetics and can influence a drug's distribution, absorption, and elimination in the body. Several factors, including the drug's physiochemical properties, protein concentration, disease states, and the number of binding sites on the protein, influence this process.
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
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Related Experiment Video

Updated: Feb 7, 2026

Real-time Analyses of Retinol Transport by the Membrane Receptor of Plasma Retinol Binding Protein
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Real-time Analyses of Retinol Transport by the Membrane Receptor of Plasma Retinol Binding Protein

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Concentration-dependent plasma protein binding: Expect the unexpected.

Roger L Nation1, Ursula Theuretzbacher2, Brian T Tsuji3

  • 1Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Melbourne, Victoria, Australia.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|July 21, 2018
PubMed
Summary
This summary is machine-generated.

Some drugs exhibit unusual concentration-dependent plasma protein binding, decreasing their unbound fraction as concentration rises. Understanding this atypical binding is crucial for drug development and clinical use.

Keywords:
Atypical concentration dependenceNonlinearityPharmacokinetic, pharmacodynamic and clinical implicationsPlasma protein bindingProposed mechanisms

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Area of Science:

  • Pharmacology
  • Drug Metabolism and Pharmacokinetics

Background:

  • The unbound fraction of a drug in plasma significantly impacts its pharmacokinetics and pharmacodynamics.
  • Nonlinear plasma protein binding, due to binding site saturation, leads to an increasing unbound fraction with rising drug concentration.
  • Atypical nonlinear binding, where the unbound fraction decreases with increasing drug concentration, is less recognized but clinically relevant.

Purpose of the Study:

  • To review drugs exhibiting atypical nonlinear plasma protein binding.
  • To present evidence and discuss proposed mechanisms for this phenomenon.
  • To explore the implications of atypical nonlinearity in drug development and clinical practice.

Main Methods:

  • Literature review of reported cases of atypical nonlinear plasma protein binding.
  • Analysis of evidence supporting the phenomenon for individual drugs.
  • Discussion of proposed mechanisms and their consistency with the law of mass action.

Main Results:

  • Several drugs demonstrate atypical nonlinear plasma protein binding, where the unbound fraction decreases as drug concentration increases.
  • The phenomenon is linked to specific drug-protein interactions and concentration-dependent binding dynamics.
  • Understanding this behavior is critical for accurate pharmacokinetic and pharmacodynamic predictions.

Conclusions:

  • Atypical nonlinear plasma protein binding is an important consideration in drug development and clinical management.
  • Early identification of this behavior is essential for optimizing dosing regimens and therapeutic drug monitoring.
  • The unexpected concentration-dependent binding observed in some drugs suggests it may occur in others, necessitating vigilance.