Blume Henning, Donath Frank, Warnke André, Schug Barbara S
SocraTec R&D GmbH, Oberursel, Germany.
Drug Saf. 2006;29(9):769-84. doi: 10.2165/00002018-200629090-00002.
Proton pump inhibitors are used extensively for the treatment of gastric acid-related disorders because they produce a greater degree and longer duration of gastric acid suppression and, thus, better healing rates, than histamine H(2) receptor antagonists. The need for long-term treatment of these disorders raises the potential for clinically significant drug interactions in patients receiving proton pump inhibitors and other medications. Therefore, it is important to understand the mechanisms for drug interactions in this setting. Proton pump inhibitors can modify the intragastric release of other drugs from their dosage forms by elevating pH (e.g. reducing the antifungal activity of ketoconazole). Proton pump inhibitors also influence drug absorption and metabolism by interacting with adenosine triphosphate-dependent P-glycoprotein (e.g. inhibiting digoxin efflux) or with the cytochrome P450 (CYP) enzyme system (e.g. decreasing simvastatin metabolism), thereby affecting both intestinal first-pass metabolism and hepatic clearance. Although interactions based on the change of gastric pH are a group-specific effect and thus may occur with all proton pump inhibitors, individual proton pump inhibitors differ in their propensities to interact with other drugs and the extent to which their interaction profiles have been defined. The interaction profiles of omeprazole and pantoprazole have been studied most extensively. A number of studies have shown that omeprazole carries a considerable potential for drug interactions, since it has a high affinity for CYP2C19 and a somewhat lower affinity for CYP3A4. In contrast, pantoprazole appears to have lower potential for interactions with other medications. Although the interaction profiles of esomeprazole, lansoprazole and rabeprazole have been less extensively investigated, evidence suggests that lansoprazole and rabeprazole seem to have a weaker potential for interactions than omeprazole. Although only a few drug interactions involving proton pump inhibitors have been shown to be of clinical significance, the potential for drug interactions should be taken into account when choosing a therapy for gastric acid-related disorders, especially for elderly patients in whom polypharmacy is common, or in those receiving a concomitant medication with a narrow therapeutic index.
质子泵抑制剂被广泛用于治疗胃酸相关疾病，因为与组胺H2受体拮抗剂相比，它们能更有效地抑制胃酸分泌，且抑制时间更长，从而治愈率更高。这些疾病的长期治疗需求增加了接受质子泵抑制剂和其他药物治疗的患者发生具有临床意义的药物相互作用的可能性。因此，了解这种情况下药物相互作用的机制很重要。质子泵抑制剂可通过提高胃内pH值改变其他药物剂型在胃内的释放情况（如降低酮康唑的抗真菌活性）。质子泵抑制剂还可通过与三磷酸腺苷依赖性P-糖蛋白相互作用（如抑制地高辛外排）或与细胞色素P450（CYP）酶系统相互作用（如降低辛伐他汀代谢）影响药物吸收和代谢，进而影响肠道首过代谢和肝脏清除率。虽然基于胃内pH值变化的相互作用是一类特异性效应，因此可能在所有质子泵抑制剂中都出现，但不同的质子泵抑制剂与其他药物相互作用的倾向以及其相互作用特征的明确程度有所不同。奥美拉唑和泮托拉唑的相互作用特征研究最为广泛。多项研究表明，奥美拉唑具有相当大的药物相互作用潜力，因为它对CYP2C19具有高亲和力，对CYP3A4的亲和力略低。相比之下，泮托拉唑与其他药物相互作用的可能性似乎较低。虽然埃索美拉唑、兰索拉唑和雷贝拉唑的相互作用特征研究较少，但有证据表明，兰索拉唑和雷贝拉唑与其他药物相互作用的潜力似乎比奥美拉唑弱。虽然只有少数涉及质子泵抑制剂的药物相互作用被证明具有临床意义，但在选择胃酸相关疾病的治疗方案时，尤其是对于常使用多种药物的老年患者或正在接受治疗指数较窄的联合用药的患者，应考虑药物相互作用的可能性。
