Abstract
The reaction of drug–protein binding is considered based on the common calculations of chemical equilibrium (using the mass action and mass balance laws) and formal chemical kinetics. The calculative and theoretical aspects presented in the review are pertinent to routine drug development. Numerous real-life examples are provided throughout the article to illustrate the practical utility of the presented concepts. This may be very helpful in the interpretation of protein binding and pharmacokinetic data. Considerable resources may be saved by the proper setting of protein binding experiments, using relatively simple calculations and estimations instead of doing experimental measurements, and also avoiding ‘improvements’ that are destined to failure. The presented material may be also useful for the simulations of pharmacokinetics and pharmacodynamics, which attempt the complete account of drug–protein binding. A complete description of the considered topics is given in the last paragraph of the Introduction
Keywords::
- affinity
- albumin
- α1-acid glycoprotein
- concentration dependence of the unbound drug fraction
- equilibrium dissociation constant
- equilibrium protein binding
- equilibrium dissociation constant
- multiple binding sites
- naproxen
- nonspecific binding
- pharmacokinetics
- protein binding kinetics
- steady state volume of distribution
- temperature dependence of protein binding
- ultrafiltration
- unbound drug fraction