M. Katashima et al., COMPARATIVE PHARMACOKINETIC-PHARMACODYNAMIC STUDY OF PROTON PUMP INHIBITORS, OMEPRAZOLE AND LANSOPRAZOLE IN RATS, Drug metabolism and disposition, 23(7), 1995, pp. 718-723
The relationship between plasma concentrations and inhibitory effects
on gastric acid secretion by omeprazole (OPZ) and lansoprazole (LPZ),
which are used as antiulcer drugs in the clinical stage, was analyzed
using the pharmaco kinetic/pharmacodynamic (PK/PD) model in rats. Afte
r intravenous administration of OPZ and LPZ (1 mg/kg), OPZ was elimina
ted 1-exponentially and LPZ was eliminated 2-exponentially from plasma
. Elimination was rapid with total body clearance of 57.6 ml/min/kg fo
r OPZ and 58.6 ml/min/kg for LPZ. The volumes of distribution at stead
y-state were 0.66 liter/kg for OPZ and 1.04 liter/kg for LPZ, and the
plasma unbound fractions were 0.105 and 0.069. The dose at which 50% o
f the maximum effect is elicited for the suppression of gastric acid s
ecretion stimulated by histamine was 0.28 +/- 0.13 mg/kg (estimated va
lue +/- SD) for OPZ and 0.18 +/- 0.03 mg/kg for LPZ. Second-order rate
constants for association of OPZ or LPZ and H+,K+-ATPase based on a P
K/PD model were 72.5 +/- 30.0 (estimated value +/- SD) and 124 +/- 58
ml/mu g/hr, respectively. Apparent turnover rate of H+,K+-ATPase was 8
.8 hr as half-life, assuming the same value for both drugs. We conclud
ed that pharmacokinetic elimination patterns of OPZ and LPZ were diffe
rent, whereas the pharmacodynamic characteristics of both drugs are ne
arly the same in rats.