Petersen K U
Institut für Pharmakologie und Toxikologie, RWTH Aachen, Germany.
Aliment Pharmacol Ther. 1995 Feb;9(1):1-9. doi: 10.1111/j.1365-2036.1995.tb00344.x.
Enzymes of the cytochrome P450 superfamily play a key role in xenobiotic metabolism. Their properties and significance are discussed with particular reference to interactions with the H+,K(+)-ATPase blocker, omeprazole. Such interactions include both inhibitory (subfamily 2C) and inducing effects (subfamily 1A). Delayed metabolic elimination of diazepam, warfarin, carbamazepin and phenytoin is probably due to omeprazole competition for the concerned isoform of subfamily 2C; however, these effects are modest to negligible in magnitude and, for phenytoin, not consistently reproducible. Also, induction of subfamily 1A is only minor as assessed from the resultant changes in N-3-demethylation of caffeine, a reaction specific to this subfamily. Concerns about a possible activation of procarcinogens that might arise from subfamily 1A induction appear ill-founded given the fact that cruciferous vegetables such as broccoli and Brussels sprouts are potent inducers, but rather seem to lower the incidence of certain types of cancer. Likewise, the idea that the toxicity of acetaminophen might increase upon subfamily 1A induction appears far-fetched, mainly because much stronger inducers of subfamily 1A (cigarette smoke and charcoaled beef) are unable to alter acetaminophen metabolism.
细胞色素P450超家族的酶在异源物质代谢中起关键作用。本文将结合与H⁺，K⁺-ATP酶阻滞剂奥美拉唑的相互作用，讨论它们的性质和意义。这种相互作用包括抑制作用（2C亚家族）和诱导作用（1A亚家族）。地西泮、华法林、卡马西平和苯妥英钠代谢消除延迟可能是由于奥美拉唑与2C亚家族相关同工型竞争；然而，这些影响程度较小甚至可忽略不计，对于苯妥英钠，其结果也并非始终可重复。此外，从咖啡因N-3-去甲基化反应（该亚家族特有的反应）的变化评估，1A亚家族的诱导作用也很轻微。鉴于西兰花和抱子甘蓝等十字花科蔬菜是强效诱导剂，但似乎能降低某些类型癌症的发病率，因此关于1A亚家族诱导可能导致致癌物前体激活的担忧似乎没有根据。同样，1A亚家族诱导会增加对乙酰氨基酚毒性的观点似乎也牵强，主要是因为更强的1A亚家族诱导剂（香烟烟雾和炭烤牛肉）无法改变对乙酰氨基酚的代谢。
