COMPARATIVE PHARMACOKINETIC PHARMACODYNAMIC ANALYSIS OF PROTON PUMP INHIBITORS OMEPRAZOLE, LANSOPRAZOLE AND PANTOPRAZOLE, IN HUMANS/

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 estimate d values of apparent reaction rate constant of PPI and H+,K+-ATPase (K ) were 1.34 +/- 0.17 (mu M-1.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, re spectively. The apparent dissociation constants of the H+,K+-ATPase-PP I complex (k/K.f(p)) corrected with plasma free fraction (f(p)) were a bout 1 nM for OPZ and LPZ and 2.3 nM for PPZ. Therefore, the potency o f the inhibitory effect of PPZ on acid secretion may be slightly weake r than that of OPZ or LPZ. The apparent half lives (ln2/k) of the inhi bitory 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 P PZ on acid secretion was slowest among these PPIs. In conclusion, the relationship between plasma concentrations and inhibitory effects of P PIs on gastric acid secretion could be analyzed by the PK/PD model.