Zhao L, Lou Y Q
Department of Pharmacology, Beijing Medical University.
Yao Xue Xue Bao. 1995;30(4):248-53.
The metabolism of omeprazole to its two major metabolites, hydroxyomeprazole (OH-OPZ) and omeprazole sulfone (OPZ-SFN) was studied in rat liver microsomes by a reversed phase HPLC assay. The formation of metabolites of OPZ depended on incubation time, substrate concentration, microsomal protein concentration, and was found to be optimal at pH 7.4. The Vmax and Km of OPZ hydroxylation in the rat liver microsomal preparation were 2033 nmol/(min.mg protein) and 46.8 mumol.L-1 respectively. The maximum rate of formation of OPZ-SFN (Vmax) was 187.9 nmol/(min.mg protein), with a Km value of 120.7 mumol.L-1 in rat liver microsome. Moreover, the effects of 7 drugs on OPZ metabolism were tested. The results showed that mephenytoin, benzodiazepines (DZ, NDZ, TMZ, FNZ, NZ) and papaverine caused inhibition of OPZ metabolism, among them papaverine was the only fairly strong inhibitor.
采用反相高效液相色谱法在大鼠肝微粒体中研究了奥美拉唑代谢生成其两种主要代谢产物——羟基奥美拉唑（OH-OPZ）和奥美拉唑砜（OPZ-SFN）的过程。OPZ代谢产物的形成取决于孵育时间、底物浓度、微粒体蛋白浓度，且发现在pH 7.4时最为适宜。大鼠肝微粒体制剂中OPZ羟基化的Vmax和Km分别为2033 nmol/（min·mg蛋白）和46.8 μmol·L⁻¹。在大鼠肝微粒体中，OPZ-SFN的最大生成速率（Vmax）为187.9 nmol/（min·mg蛋白），Km值为120.7 μmol·L⁻¹。此外，测试了7种药物对OPZ代谢的影响。结果表明，美芬妥英、苯二氮䓬类药物（DZ、NDZ、TMZ、FNZ、NZ）和罂粟碱可抑制OPZ代谢，其中罂粟碱是唯一一种抑制作用较强的药物。
