Fig. 12.

The influence of pH and pK_a on drug distribution. Theoretical distribution of a hypothetical weakly acidic drug (pK_a = 3.4, panel ‘A’) and a hypothetical weakly basic drug (pK_a = 8.4, panel ‘B’) between two aqueous compartments with different pH (GI tract at pH = 1.4 and blood at pH = 7.4). Assuming that only the unionized form U (HA in panel ‘A’ and B in panel ‘B’) can cross the membrane and that U is equilibrated across the plasma membrane, panel ‘A’ shows that a weakly acidic drug is more concentrated in the alkaline compartment. This result suggests that weakly acidic drugs tend to be absorbed from the more acidic compartment to the more basic compartment (blue arrows). Panel ‘B’ shows that a weakly basic drug is more concentrated in the acidic compartment, indicating that weakly basic drugs are poorly absorbed in an acidic compartment (blue arrows). Weakly basic drugs are in fact poorly absorbed from the stomach. GI: gastrointestinal; Bl: blood. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)