Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
J Gastroenterol Hepatol. 2013 Dec;28(12):1823-8. doi: 10.1111/jgh.12305.
Esomeprazole provides effective and long lasting inhibition of gastric acid secretion. However, the pharmacokinetics and pharmacodynamics of intravenous esomeprazole in the Chinese population remain unclear.
To compare the pharmacokinetics and pharmacodynamics of intravenous esomeprazole (injection and infusion) and their clinical safety and tolerability in healthy Chinese subjects.
A randomized, single-center, open-label, five-way crossover study was conducted in 20 healthy volunteers. CYP2C19 metabolizer genotype and Helicobacter pylori status were examined. Five dosing regimens were used: single 40 mg injection, 40 mg infusion every 12 h, 40 mg infusion followed by continuous infusion at 8 mg/h, 80 mg infusion followed by continuous infusion at 4 or 8 mg/h. Intragastric pH was recorded within 24 h. Plasma concentration-time curve, maximum plasma concentration (Cmax ), steady state concentration, and total plasma clearance were determined. Adverse events were also recorded.
Continuous infusion resulted in a higher mean area under the curve and Cmax than injection. There were no significant differences among the four infusion groups in terms of percentages of time at pH > 4, > 5, > 6, > 7 within 24 h and pH > 6 within the first 3 h. There were no significant differences in pharmacokinetic or pH values among variants of CYP2C19 genotype. The pH value within 24 h was unaffected by H. pylori infection in subjects with continuous infusion.
Esomeprazole administrated by infusion produces better pharmacokinetic and intragastric pH profiles compared with those by injection. The optimal administration schedule for esomeprazole in Chinese subjects is infusion with 40 mg/12 h.
埃索美拉唑可有效且持久地抑制胃酸分泌。然而，埃索美拉唑静脉给药在中国人群中的药代动力学和药效动力学特征尚不清楚。
比较健康中国受试者中静脉注射和输注埃索美拉唑的药代动力学和药效动力学，以及其临床安全性和耐受性。
这是一项在 20 名健康志愿者中进行的随机、单中心、开放标签、五交叉研究。检测了 CYP2C19 代谢物基因型和幽门螺杆菌状态。使用了 5 种给药方案：单次 40mg 注射、每 12h 40mg 输注、40mg 输注后以 8mg/h 持续输注、80mg 输注后以 4 或 8mg/h 持续输注。在 24 小时内记录胃内 pH 值。测定了血浆浓度-时间曲线、最大血浆浓度（Cmax）、稳态浓度和总血浆清除率。还记录了不良事件。
持续输注的平均曲线下面积和 Cmax 均高于注射。在 4 种输注组中，24 小时内 pH 值>4、>5、>6、>7的时间百分比以及前 3 小时内 pH 值>6的时间百分比无显著差异。CYP2C19 基因型变异体之间的药代动力学或 pH 值无显著差异。在接受持续输注的受试者中，幽门螺杆菌感染对 24 小时内的 pH 值无影响。
与注射相比，埃索美拉唑输注给药可产生更好的药代动力学和胃内 pH 谱。埃索美拉唑在中国受试者中的最佳给药方案为 40mg/12h 输注。
