Gastric
pH is an important factor that
affects drug absorption, as gastric
pH may
lead to lower
bioavailability, especially for weak-base
drugs.
Acid-
reducing agents (ARAs) such as
antacids,
histamine-2 receptor antagonists, and
proton pump inhibitors, are susceptible to
drug-
drug interactions (DDIs), potentially resulting in the loss of
efficacy. Physiologically based pharmacokinetic (PBPK) modeling is an important tool for the evaluation of oral
drug-
drug interactions and the most commonly used models include the advanced comparative
absorption and transport (ACAT) model and the advanced
dissolution,
absorption and
metabolism (ADAM) model. These models can be used for
adjustment of the
dosage regimen and the
screening of candidate
drugs in
drug development by simulating the change of gastric
pH to predict the change in
drug absorption. This
review summarizes the theoretical basis, the most common PBPK models used to predict
drug absorption, and the effects of different kinds of ARAs
drugs on gastric
pH. Some successful applications of PBPK modeling in predicting the effects of gastric
pH on
drug absorption are also presented.