一日四次服用雷贝拉唑进行一日预负荷给药，随后采用标准的每日两次给药方案，可为CYP2C19的广泛代谢者提供足够的胃酸抑制作用。
One-day front-loading with four doses of rabeprazole followed by a standard twice-daily regimen provides sufficient acid inhibition in extensive metabolizers of CYP2C19.
作者信息
Kagami Takuma, Sugimoto Mitsushige, Ichikawa Hitomi, Sahara Shu, Uotani Takahiro, Yamade Mihoko, Hamaya Yasushi, Iwaizumi Moriya, Osawa Satoshi, Sugimoto Ken, Miyajima Hiroaki, Furuta Takahisa
机构信息
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Clinical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
出版信息
Eur J Clin Pharmacol. 2015 Dec;71(12):1467-75. doi: 10.1007/s00228-015-1941-9. Epub 2015 Oct 2.
BACKGROUND
Four times daily dosing (qid) with a proton pump inhibitor can cause rapid increase in intragastric pH. We investigated the efficacy of the front-loading with rabeprazole 10 mg qid on a subsequent regimen with rabeprazole 10 mg twice daily (bid) for 7 days in extensive metabolizers (EMs) of CYP2C19.
METHODS
Five EMs received three different 1-week regimens in a crossover manner as follows: (1) rabeprazole 10 mg bid for 7 days; (2) a front-loading regimen of rabeprazole (rabeprazole 10 mg qid on day 0 and bid on days 1 to 7); and (3) rabeprazole 10 mg qid for 7 days. Five intermediate metabolizers (IMs) and four poor metabolizers (PMs) received rabeprazole 10 mg bid regimen only. Twenty-four-hour intragastric pH-monitorings were performed on days 1, 4, and 7. Area under the intragastric pH-time curves (AUCs) from days 1 to 7 was calculated using 24-h median intragastric pHs on days 1, 4, and 7.
RESULTS
Twenty-four-hour intragastric pHs in the front-loading group on days 1, 4, and 7 were 5.1, 4.9, and 5.1, respectively. The median AUC with front-loading in EMs (34.4, pH·day) was significantly higher than that in EMs with rabeprazole 10 mg bid (30.74, p = 0.043). No statistically significant differences in median AUCs were noted among front-loading in EMs, rabeprazole 10 mg qid in EMs (37.2), rabeprazole 10 mg bid in IMs (37.3), and PMs (39.4).
CONCLUSIONS
The one-day front-loading regimen of rabeprazole 10 mg qid provided sufficient acid inhibition for 7 days, even in CYP2C19 EMs.
背景
质子泵抑制剂每日四次给药（qid）可使胃内pH值迅速升高。我们研究了在CYP2C19广泛代谢者（EMs）中，先给予雷贝拉唑10mg每日四次进行预负荷，随后给予雷贝拉唑10mg每日两次（bid）持续7天的方案的疗效。
方法
5名EMs以交叉方式接受三种不同的1周治疗方案，如下：（1）雷贝拉唑10mg bid，持续7天；（2）雷贝拉唑预负荷方案（第0天雷贝拉唑10mg qid，第1至7天bid）；（3）雷贝拉唑10mg qid，持续7天。5名中间代谢者（IMs）和4名慢代谢者（PMs）仅接受雷贝拉唑10mg bid方案。在第1、4和7天进行24小时胃内pH监测。使用第1、4和7天的24小时胃内pH中位数计算第1至7天胃内pH -时间曲线下面积（AUCs）。
结果
预负荷组第1、4和7天的24小时胃内pH值分别为5.1、4.9和5.1。EMs中预负荷的中位AUC（34.4，pH·天）显著高于雷贝拉唑10mg bid的EMs（30.74，p = 0.043）。在EMs中的预负荷、EMs中雷贝拉唑10mg qid（37.2）、IMs中雷贝拉唑10mg bid（37.3）和PMs（39.4）之间，中位AUCs无统计学显著差异。
结论
即使在CYP2C19 EMs中，雷贝拉唑10mg qid的一日预负荷方案也能提供足够的抑酸作用达7天。
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