The relationship between plasma concentrations and inhibitory effects on gastric acid secretion by proton pump inhibitors (PPIs) omeprazole (OPZ), lansoprazole (LPZ) and pantoprazole (PPZ), was analyzed using a pharmacokinetic/pharmacodynamic (PK/PD) model in humans. The estimated values of apparent reaction rate constant of PPI and H+,K+-ATPase (K) were 1.34 +/- 0.17 (microM(-1) x h(-1)), 0.339 +/- 0.002 and 0.134 +/- 0.006 for OPZ, LPZ and PPZ, respectively. The estimated values of apparent turn-over rate constant of H+,K+-ATPase (k) were 0.0252 +/- 0.0019 (h(-1)), 0.0537 +/- 0.0006 and 0.0151 +/- 0.0002 for OPZ, LPZ and PPZ, respectively. The apparent dissociation constants of the H+,K+-ATPase-PPI complex (k/K x fp) corrected with plasma free fraction (fp) were about 1 nM for OPZ and LPZ and 2.3 nM for PPZ. Therefore, the potency of the inhibitory effect of PPZ on acid secretion may be slightly weaker than that of OPZ or LPZ. The apparent half lives (ln2/k) of the inhibitory effect on acid secretion were 12.9 h for LPZ, < 27.5 h for OPZ, and < 45.9 h for PPZ, the recovery rate of the inhibitory effect of PPZ on acid secretion was slowest among these PPIs. In conclusion, the relationship between plasma concentrations and inhibitory effects of PPIs on gastric acid secretion could be analyzed by the PK/PD model.