Katashima M, Yamamoto K, Sugiura M, Sawada Y, Iga T
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Drug Metab Dispos. 1995 Jul;23(7):718-23.
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.
使用大鼠的药代动力学/药效学（PK/PD）模型，分析了在临床阶段用作抗溃疡药物的奥美拉唑（OPZ）和兰索拉唑（LPZ）的血浆浓度与胃酸分泌抑制作用之间的关系。静脉注射OPZ和LPZ（1mg/kg）后，OPZ从血浆中呈一级指数消除，LPZ呈二级指数消除。消除迅速，OPZ的全身清除率为57.6ml/min/kg，LPZ为58.6ml/min/kg。稳态分布容积OPZ为0.66升/kg，LPZ为1.04升/kg，血浆未结合分数分别为0.105和0.069。对于组胺刺激的胃酸分泌抑制作用，引起最大效应50%的剂量，OPZ为0.28±0.13mg/kg（估计值±标准差），LPZ为0.18±0.03mg/kg。基于PK/PD模型，OPZ或LPZ与H⁺，K⁺-ATP酶结合的二级速率常数分别为72.5±30.0（估计值±标准差）和124±58ml/μg/hr。假设两种药物的H⁺，K⁺-ATP酶的表观周转率相同，半衰期为8.8小时。我们得出结论，OPZ和LPZ的药代动力学消除模式不同，而两种药物在大鼠中的药效学特征几乎相同。
