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Abstract

Comparative pharmacokinetic/pharmacodynamic study of proton pump inhibitors, omeprazole and lansoprazole in rats.

M Katashima, K Yamamoto, M Sugiura, Y Sawada and T Iga
Drug Metabolism and Disposition July 1995, 23 (7) 718-723;
M Katashima
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K Yamamoto
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M Sugiura
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Y Sawada
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T Iga
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Abstract

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 pharmacokinetic/pharmacodynamic (PK/PD) model in rats. After intravenous administration of OPZ and LPZ (1 mg/kg), OPZ was eliminated 1-exponentially and LPZ was eliminated 2-exponentially from plasma. Elimination was rapid with total body clearance of 57.6 ml/min/kg for OPZ and 58.6 ml/min/kg for LPZ. The volumes of distribution at steady-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% of the maximum effect is elicited for the suppression of gastric acid secretion stimulated by histamine was 0.28 +/- 0.13 mg/kg (estimated value +/- 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 PK/PD model were 72.5 +/- 30.0 (estimated value +/- SD) and 124 +/- 58 ml/micrograms/hr respectively. Apparent turnover rate of H+,K+-ATPase was 8.8 hr as half-life, assuming the same value for both drugs. We concluded that pharmacokinetic elimination patterns of OPZ and LPZ were different, whereas the pharmacodynamic characteristics of both drugs are nearly the same in rats.

 

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Drug Metabolism and Disposition
Vol. 23, Issue 7
1 Jul 1995
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Abstract

Comparative pharmacokinetic/pharmacodynamic study of proton pump inhibitors, omeprazole and lansoprazole in rats.

M Katashima, K Yamamoto, M Sugiura, Y Sawada and T Iga
Drug Metabolism and Disposition July 1, 1995, 23 (7) 718-723;

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Abstract

Comparative pharmacokinetic/pharmacodynamic study of proton pump inhibitors, omeprazole and lansoprazole in rats.

M Katashima, K Yamamoto, M Sugiura, Y Sawada and T Iga
Drug Metabolism and Disposition July 1, 1995, 23 (7) 718-723;
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