pKa

For drugs that exist as a weak acid or weak base, an equilibrium exists between charged and uncharged forms of the molecule:

AH ↔ H⁺ + A^– (acid)        B + H⁺ ↔ BH⁺ (base)

The pK_a is the pH at which 50% of the drug is ionised (charged) and 50% is uncharged. The proportion of drug that is charged depends on the pH of the local aqueous environment, on the pK_a for that drug, and on whether the drug is an acid or a base. This proportion can be determined with the Henderson-Hasselbalch equation.

The pharmacokinetic importance of this ratio is that generally, only uncharged drug (in this example, either AH or B) can diffuse across cell membranes (lipid bilayers) easily.