Masubuchi N, Okazaki O
Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Chem Biol Interact. 1997 Nov 6;107(1-2):63-74. doi: 10.1016/s0009-2797(97)00074-4.
The ability of pantoprazole to affect the induction of cytochrome P450 (CYP) 1A subfamily was evaluated and compared with two other proton pump inhibitors, omeprazole and lansoprazole, in primary cultured hepatocytes from female Sprague-Dawley rats. The hepatocytes were cultured for 2 days, followed by treatment for 2 days with the proton pump inhibitors at 2, 5 and 10 microM, concentrations that are similar to plasma concentrations found in rats in vivo. The CYP1A inducer 3-methylcholanthrene (at 1 microM) was also evaluated as a positive control. Induction potentials of these chemicals for CYP1A were determined by 7-ethoxyresorufin O-deethylase activity and isozyme contents. The results showed that for CYP1A induction, the rank ordering in induction potential was consistently lansoprazole > omeprazole > pantoprazole. The results are consistent with the existing rat in vivo data, i.e. pantoprazole has lower CYP1A induction potential than omeprazole and lansoprazole.
在来自雌性斯普拉格-道利大鼠的原代培养肝细胞中，评估了泮托拉唑影响细胞色素P450（CYP）1A亚家族诱导的能力，并与另外两种质子泵抑制剂奥美拉唑和兰索拉唑进行了比较。将肝细胞培养2天，然后用浓度为2、5和10微摩尔的质子泵抑制剂处理2天，这些浓度与大鼠体内发现的血浆浓度相似。CYP1A诱导剂3-甲基胆蒽（1微摩尔）也作为阳性对照进行了评估。通过7-乙氧基异吩恶唑酮O-脱乙基酶活性和同工酶含量来确定这些化学物质对CYP1A的诱导潜力。结果表明，对于CYP1A诱导，诱导潜力的排序始终是兰索拉唑>奥美拉唑>泮托拉唑。这些结果与现有的大鼠体内数据一致，即泮托拉唑的CYP1A诱导潜力低于奥美拉唑和兰索拉唑。
