Andersson T
Department of Clinical Pharmacology, Hässle Research Laboratories, Mölndal, Sweden.
Clin Pharmacokinet. 1991 Sep;21(3):195-212. doi: 10.2165/00003088-199121030-00004.
This review examines the literature on drug interactions with omeprazole. Different mechanisms have been proposed as potential causes for such interactions. First, the absorption of some drugs might be altered due to the decreased intragastric acidity resulting from omeprazole treatment. There was no effect of omeprazole on the absorption of amoxycillin, bacampicillin and alcohol, while the amount of digoxin and nifedipine absorbed was increased by 10 and 21%, respectively, both increases probably being of no clinical significance. Secondly, the metabolism of high clearance drugs might be altered by changes in liver blood flow, although that is not affected by omeprazole, as indicated by the unchanged elimination of indocyanine green. In addition, the clearance of intravenously administered lidocaine (lignocaine) [a high clearance drug] was unaffected by omeprazole, further indicating that the latter does not alter liver blood flow. Thirdly, since omeprazole is a substituted benzimidazole, it might have the potential to interfere with the metabolism of other drugs by altering the activity of drug metabolising enzymes in the cytochrome P450 system, through either induction or inhibition. There is no indication of induction of this enzyme system in any interaction study with omeprazole. As regards inhibition, on the other hand, there is now considerable information available which indicates that omeprazole has the potential to partly inhibit the metabolism of drugs metabolised to a great extent by the cytochrome P450 enzyme subfamily IIC (diazepam, phenytoin), but not of those metabolised by subfamilies IA (caffeine, theophylline), IID (metoprolol, propranolol) and IIIA (cyclosporin, lidocaine, quinidine). Since relatively few drugs are metabolised mainly by IIC compared with IID and IIIA, the potential for omeprazole to interfere with the metabolism of other drugs appears to be limited.
本综述研究了有关药物与奥美拉唑相互作用的文献。已提出不同机制作为此类相互作用的潜在原因。首先，由于奥美拉唑治疗导致胃内酸度降低，一些药物的吸收可能会发生改变。奥美拉唑对阿莫西林、巴卡西林和酒精的吸收没有影响，而地高辛和硝苯地平的吸收量分别增加了10%和21%，这两种增加可能都没有临床意义。其次，高清除率药物的代谢可能会因肝血流量的变化而改变，尽管如吲哚菁绿清除率未变所示，奥美拉唑对此没有影响。此外，静脉注射利多卡因（一种高清除率药物）的清除率不受奥美拉唑影响，这进一步表明后者不会改变肝血流量。第三，由于奥美拉唑是一种取代苯并咪唑，它可能有潜力通过诱导或抑制作用改变细胞色素P450系统中药物代谢酶的活性，从而干扰其他药物的代谢。在任何与奥美拉唑的相互作用研究中，均未显示该酶系统有诱导作用。另一方面，关于抑制作用，现在有大量信息表明，奥美拉唑有潜力部分抑制主要由细胞色素P450酶亚家族IIC代谢的药物（地西泮、苯妥英）的代谢，但对由亚家族IA（咖啡因、茶碱）、IID（美托洛尔、普萘洛尔）和IIIA（环孢素、利多卡因、奎尼丁）代谢的药物没有影响。与IID和IIIA相比，主要由IIC代谢的药物相对较少，因此奥美拉唑干扰其他药物代谢的可能性似乎有限。
