Oosterhuis B, Jonkman J H
Pharma Bio-Research International BV, Assen, The Netherlands.
Digestion. 1989;44 Suppl 1:9-17. doi: 10.1159/000200098.
Omeprazole is a prodrug which is converted to its active form only at the site of action, namely the parietal cell. There it binds irreversibly with H+-K+-ATPase (the gastric proton pump), which causes an effective and long-lasting inhibition of gastric acid secretion. The pharmacokinetic profile of omeprazole is rather complicated, showing concentration-dependent elimination kinetics and an oral bioavailability which increases with the dose and during repeated administration. For the choice of dosage regimens this has minor consequences, in view of the wide therapeutic range of omeprazole and because an almost continuous maximum effect is obtained with once daily oral administration of 20-40 mg. Omeprazole may influence the pharmacokinetics of concurrently administered drugs by an inhibition of their oxidative metabolism. For most drugs studied thus far, the influence is less or even negligible in comparison with the influence of cimetidine, with the exception of diazepam. For every new combination of omeprazole with a drug that has a critical therapeutic range the consequences of a possible interaction should be studied.
奥美拉唑是一种前体药物，仅在作用部位即壁细胞内转化为其活性形式。在壁细胞内，它与H⁺-K⁺-ATP酶（胃质子泵）不可逆结合，从而有效且持久地抑制胃酸分泌。奥美拉唑的药代动力学特征相当复杂，呈现浓度依赖性消除动力学，口服生物利用度随剂量增加以及重复给药而提高。鉴于奥美拉唑的治疗范围广，且每日口服20 - 40 mg几乎能持续获得最大疗效，这对给药方案的选择影响较小。奥美拉唑可能通过抑制同时服用药物的氧化代谢而影响其药代动力学。对于迄今研究的大多数药物，与西咪替丁的影响相比，其影响较小甚至可忽略不计，但地西泮除外。对于奥美拉唑与治疗范围狭窄的药物的每一种新组合，都应研究可能相互作用的后果。
