Andersson T
Astra Hässle, Mölndal, Sweden.
Clin Pharmacokinet. 1996 Jul;31(1):9-28. doi: 10.2165/00003088-199631010-00002.
This review updates and evaluates the currently available information regarding the pharmacokinetics, metabolism and interactions of the acid pump inhibitors omeprazole, lansoprazole and pantoprazole. Differences and similarities between the compounds are discussed. Omeprazole, lansoprazole and pantoprazole are all mainly metabolished by the polymorphically expressed cytochrome P450 (CYP) isoform S-mephenytoin hydroxylase (CYP2C19), which means that within a population a few individuals (3% of Caucasians) metabolise the compounds slowly compared with the majority of the population. For all 3 compounds, the area under the plasma concentration-versus-time curve (AUC) for a slow metaboliser is, in general, approximately 5 times higher than that in an average patient. Since all 3 compounds are considered safe and well tolerated, and no dosage-related adverse drug reactions have been identified, this finding seems to be of no clinical relevance. The acid pump inhibitors seem to be similarly handled in the elderly, where a somewhat slower elimination can be demonstrated compared with young individuals. In patients with renal insufficiency, omeprazole is eliminated as in healthy individuals, whereas the data on lansoprazole and pantoprazole are unresolved. In patients with hepatic insufficiency, as expected, the elimination rates of all 3 compounds are substantially decreased. No clinically relevant effects on specific endogenous glandular functions, such as the adrenal (cortisol), the gonads or the thyroid, were demonstrated for omeprazole and pantoprazole, whereas a few minor concerns have been raised regarding lansoprazole. The absorption of some compounds, e.g. digoxin, might be altered as a result of the increased gastric pH obtained during treatment with acid pump inhibitors, and, accordingly, similar effects are expected irrespective of which acid pump inhibitor is given. The effect of the acid pump inhibitors on enzymes in the liver has been intensely debated, and some authors have claimed that lansoprazole and pantoprazole have less potential than omeprazole to interact with other drugs metabolised by CYP. However, after assessment of available data in this area, the conclusion is that all 3 acid pump inhibitors have a very limited potential for drug interactions at the CYP level. In addition, the small effects on CYP reported for these compounds are rarely of any clinical relevance, considering the normal intra- (and inter-)individual variations in metabolism observed for most drugs. In conclusion, omeprazole, lansoprazole and pantoprazole are structurally very similar, and an evaluation of available data indicates that also with respect to pharmacokinetics, metabolism and interactions in general they demonstrate very similar properties, even though omeprazole has been more thoroughly studied with regard to different effects.
本综述更新并评估了目前有关酸泵抑制剂奥美拉唑、兰索拉唑和泮托拉唑的药代动力学、代谢及相互作用的可用信息。讨论了这些化合物之间的异同。奥美拉唑、兰索拉唑和泮托拉唑主要均由具有多态性表达的细胞色素P450（CYP）同工酶S - 美芬妥因羟化酶（CYP2C19）代谢，这意味着在人群中，少数个体（3%的高加索人）与大多数人相比，对这些化合物的代谢较慢。对于所有这3种化合物，慢代谢者的血浆浓度 - 时间曲线下面积（AUC）通常比普通患者高约5倍。由于这3种化合物都被认为是安全且耐受性良好的，并且尚未发现与剂量相关的药物不良反应，这一发现似乎并无临床相关性。酸泵抑制剂在老年人中的处理方式似乎相似，与年轻人相比，其消除速度稍慢。在肾功能不全患者中，奥美拉唑的消除与健康个体相同，而关于兰索拉唑和泮托拉唑的数据尚无定论。在肝功能不全患者中，正如预期的那样，所有3种化合物的消除率均大幅降低。对于奥美拉唑和泮托拉唑，未显示对特定内分泌腺功能（如肾上腺（皮质醇）、性腺或甲状腺）有临床相关影响，而关于兰索拉唑则提出了一些小问题。某些化合物（如地高辛）的吸收可能会因酸泵抑制剂治疗期间胃pH值升高而改变，因此，无论使用哪种酸泵抑制剂，预计都会有类似效果。酸泵抑制剂对肝脏酶的影响一直存在激烈争论，一些作者声称兰索拉唑和泮托拉唑与其他由CYP代谢的药物相互作用的可能性比奥美拉唑小。然而，在评估该领域的现有数据后，得出的结论是，所有3种酸泵抑制剂在CYP水平上药物相互作用的可能性非常有限。此外，考虑到大多数药物在代谢方面正常的个体内（和个体间）差异，这些化合物对CYP报道的微小影响很少具有临床相关性。总之，奥美拉唑、兰索拉唑和泮托拉唑在结构上非常相似，对现有数据的评估表明，即使奥美拉唑在不同作用方面的研究更为深入，但在药代动力学、代谢及相互作用总体方面，它们也表现出非常相似的特性。
