Thjodleifsson Bjarni
Department of Medicine, University Hospital, Reykjavik, Iceland.
Drugs Aging. 2002;19(12):911-27. doi: 10.2165/00002512-200219120-00003.
Proton pump inhibitors (PPIs) have revolutionised the treatment of acid-related disorders, and they have also made it possible to define the spectrum of acid inhibition required for optimal treatment in each disorder. Five PPIs are now available: the older drugs, omeprazole, lansoprazole and pantoprazole, and the two newest, rabeprazole and esomeprazole. These agents have predominantly been developed in the younger adult population, and data for the elderly population are limited. Subtle differences have emerged between the old and the new PPIs in their pharmacokinetic, pharmacodynamic and efficacy profiles. The degree of clinical relevance of these differences in the adult population is in question. However, according to this review, based on the available data for the elderly and by inference from the adult population, the differences are highly relevant in the elderly population. Studies of the pharmacokinetics of older PPIs demonstrated considerable variation in drug clearance that was reflected in a wide range of efficacy related to acid suppression with standard dosages. The newer PPIs offer several advantages over older agents, particularly in terms of rapid, profound and consistent acid inhibition. Consistent acid inhibition is particularly important in the elderly since clinical response is often difficult to judge in this patient group. An individual's cytochrome P450 (CYP) 2C19 genotype predicts the degree of acid suppression and consequently the clinical efficacy of the PPIs. The older PPIs are predominantly metabolised by CYP2C19, with this being of more importance for omeprazole and lansoprazole than pantoprazole. The hepatic metabolism of rabeprazole is predominantly by nonenzymatic reactions and minimally by CYP-mediated reactions, which therefore confers an advantage over older PPIs in that genetic polymorphisms for CYP2C19 do not significantly influence rabeprazole clearance, clinical efficacy or potential for drug interactions. The metabolism of esomeprazole involves CYP2C19 but to a lesser extent than its predecessor omeprazole. Furthermore, esomeprazole has a more rapid onset of action and less variation in clearance rates than omeprazole. Drug clearance decreases with age independently of CYP2C19 status, exaggerating some of the differences between the PPIs and increasing the risk of drug interactions.
质子泵抑制剂（PPIs）彻底改变了酸相关性疾病的治疗方式，也使得确定每种疾病最佳治疗所需的酸抑制范围成为可能。目前有五种PPIs可供使用：较老的药物奥美拉唑、兰索拉唑和泮托拉唑，以及两种最新的药物雷贝拉唑和埃索美拉唑。这些药物主要是在年轻成年人群中研发的，老年人群的数据有限。新旧PPIs在药代动力学、药效学和疗效方面已出现细微差异。这些差异在成年人群中的临床相关性程度尚不确定。然而，根据本综述，基于老年人群的现有数据并从成年人群推断，这些差异在老年人群中具有高度相关性。对较老PPIs药代动力学的研究表明，药物清除率存在相当大的差异，这反映在标准剂量下与酸抑制相关的广泛疗效范围内。较新的PPIs比较老的药物具有几个优势，特别是在快速、强效和持续的酸抑制方面。持续的酸抑制在老年人中尤为重要，因为在这个患者群体中临床反应往往难以判断。个体的细胞色素P450（CYP）2C19基因型可预测酸抑制程度，从而预测PPIs的临床疗效。较老的PPIs主要由CYP2C19代谢，这对奥美拉唑和兰索拉唑比对泮托拉唑更为重要。雷贝拉唑的肝脏代谢主要通过非酶反应，极少通过CYP介导的反应，因此与较老的PPIs相比具有优势，因为CYP2C19的基因多态性不会显著影响雷贝拉唑的清除率、临床疗效或药物相互作用的可能性。埃索美拉唑的代谢涉及CYP2C19，但程度低于其前身奥美拉唑。此外，埃索美拉唑的起效更快，清除率的变化比奥美拉唑更小。药物清除率随年龄增长而降低，与CYP2C19状态无关，这放大了PPIs之间的一些差异，并增加了药物相互作用的风险。
