Kromer W
Department of Pharmacology, Byk Gulden, Konstanz, Germany.
Digestion. 1995;56(6):443-54. doi: 10.1159/000201275.
The novel antiulcer drugs omeprazole, lansoprazole, and pantoprazole are members of the class of substituted benzimidazoles. They potently inhibit the gastric proton pump by a common mechanism which depends on the acid-induced conversion of the parent compounds to the pharmacologically active principles: thiophilic cyclic sulfenamides. This transformation takes place in the luminal compartment of the secreting parietal cell. However, while the three proton pump inhibitors belong to the same chemical class, their two ring systems bear different functional substituents. This leads to essential modification of the physiochemical, metabolic, and pharmacokinetic properties of these drugs, possibly resulting in differences in tissue selectivity and thereby, in the long term, drug safety. Both preclinical and clinical data have accumulated that point to advantages of pantoprazole related to the above parameters: pantoprazole shows a higher stability at moderately acidic pH values and less inhibitory potential against cytochrome P450 than the other two drugs. In addition, pantoprazole displays linear pharmacokinetics with a high bioavailability.
新型抗溃疡药物奥美拉唑、兰索拉唑和泮托拉唑属于取代苯并咪唑类。它们通过一种共同机制强力抑制胃质子泵，该机制依赖于母体化合物在酸诱导下转化为药理活性成分：亲硫性环状亚磺酰胺。这种转化发生在分泌性壁细胞的管腔隔室中。然而，虽然这三种质子泵抑制剂属于同一化学类别，但它们的两个环系统带有不同的官能取代基。这导致这些药物的物理化学、代谢和药代动力学性质发生本质改变，可能导致组织选择性差异，从而从长远来看影响药物安全性。临床前和临床数据均已积累，表明泮托拉唑在上述参数方面具有优势：与其他两种药物相比，泮托拉唑在中等酸性pH值下显示出更高的稳定性，对细胞色素P450的抑制潜力更小。此外，泮托拉唑具有线性药代动力学和高生物利用度。
