pKa is the acid dissociation constant, which describes the acidity of a particular molecule. The lower the value of pKa, the stronger the acid and the greater its ability to donate its protons (see blog “What is pKa and how is it used in drug development?”)
However, in biorelevant environments, the degree of ionization of a drug will not only be determined by the acid/base equilibrium of the drug (pKa), but also by parallel equilibria. These can arise from the interactions of the drug with the different components of the media such as different types of micelles, surfactants or even components of the buffer solution.
To understand these complex interactions, we need to determine the “apparent dissociation constant” (pKa’) in these environments directly, to capture the influence of parallel equilibria on the dissociation constant of the drug (pKa). In other words, comparison of the pKa values obtained for the apparent dissociation constant (pKa’) and the dissociation constant of the drug in water(pKa) will provide information about additional interactions with the medium upon the ionization of the drug.
It is well known that the pKa value of a compound is important in ADME processes, because it not only determines the degree of ionization in a given environment, but it also influences other properties of the compound, such as permeability, solubility and lipophilicity. As the pKa of a compound can be influenced by the medium, the apparent dissociation constant pKa’ should be used instead to obtain a better understanding of the physicochemical properties of the drugs under biorelevant conditions.
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