Arnold R, Koop H
Department of Internal Medicine, Philipps University, Marburg, FRG.
Digestion. 1989;44 Suppl 1:77-86. doi: 10.1159/000200107.
Based on the experience from more than 10,000 individuals omeprazole has been found to be safe and is well tolerated. Side effects are few and do not differ from those observed during H2-blocker treatment. Effects on endocrine cells observed in animals during toxicological studies include increase of antral G cells, decrease of antral D cells and increase of fundic ECL cells. The increase of G cells and the decrease of D cells is the consequence of achlorhydria achieved by very high omeprazole dosages and results in hypergastrinaemia. Hypergastrinaemia is responsible for ECL cell hyperplasia. Lifelong hypergastrinaemia in rats has been found to induce carcinoid tumours. This gastrin-carcinoid sequence is unlikely to occur in man with an omeprazole dosage recommended for treatment of peptic diseases. Therapeutic doses in man do not produce complete achlorhydria. Therefore, serum gastrin levels increase in man during omeprazole treatment only moderately and are similar in magnitude as after selective proximal vagotomy. Available results on gastric endocrine cells in patients treated with omeprazole for up to 2 years could not demonstrate significant changes in G, D and ECL cell densities. It is concluded that omeprazole is, in man, as safe as H2 blockers if administered in doses recommended for treatment of peptic diseases.
基于对一万多名个体的研究经验，已发现奥美拉唑是安全的，且耐受性良好。副作用很少，与H2受体阻滞剂治疗期间观察到的副作用并无差异。毒理学研究中在动物身上观察到的对内分泌细胞的影响包括胃窦G细胞增多、胃窦D细胞减少以及胃底肠嗜铬样（ECL）细胞增多。G细胞增多和D细胞减少是高剂量奥美拉唑导致胃酸缺乏的结果，进而引起高胃泌素血症。高胃泌素血症是ECL细胞增生的原因。已发现大鼠终身高胃泌素血症会诱发类癌肿瘤。在按照治疗消化性疾病推荐剂量使用奥美拉唑的人类中，这种胃泌素 - 类癌序列不太可能发生。人类的治疗剂量不会导致完全胃酸缺乏。因此，在奥美拉唑治疗期间，人类血清胃泌素水平仅适度升高，且升高幅度与选择性近端迷走神经切断术后相似。对使用奥美拉唑治疗长达2年的患者胃内分泌细胞的现有研究结果未能证明G、D和ECL细胞密度有显著变化。结论是，在人类中，如果按照治疗消化性疾病的推荐剂量给药，奥美拉唑与H2受体阻滞剂一样安全。
