Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Department of Statistics, APACE, Seoul, Republic of Korea.
Drug Des Devel Ther. 2023 Feb 15;17:497-506. doi: 10.2147/DDDT.S391716. eCollection 2023.
Proton pump inhibitors (PPIs) are the first-line therapy for gastroesophageal reflux disorder (GERD). Unlike conventional PPIs, non-enteric coated PPIs with antacid salt enable a faster acid suppression through the rapid absorption of the PPI. YPI-011 is a newly developed fixed-dose combination of a rabeprazole with sodium bicarbonate (NaHCO). This study compared the pharmacokinetics (PKs) and pharmacodynamics (PDs) of YPI-011 to the conventional enteric-coated rabeprazole (Pariet).
A randomized, open-label, two-treatment, two-sequence crossover study was conducted with two different doses (10 and 20 mg) and 44 subjects in each group. They randomly received either a test or reference treatment for 7 days in the first period and the other treatment in the second period. Blood samples for the PK analysis were taken after the single- and multiple-dose. Intragastric pH monitoring for the PD analysis was implemented for baseline and after the single- and multiple-dose.
Gastric acid suppression evaluated by the percentage decrease from baseline in the integrated gastric acidity for a 24-hour interval after the multiple-dose was similar between the treatments in both dose groups. The systemic exposure of rabeprazole at steady state after the multiple-dose was also similar between the treatments in both dose groups. The time to reach the maximum rabeprazole concentration was faster in the test treatment. The PK-PD relationship of PPI is well known, and the faster absorption of rabeprazole resulted in a more rapid mode of action in acid suppression.
The fixed dose combination of rabeprazole with NaHCO showed a faster absorption and consequently, a more rapid gastric acid suppression with a similar systemic exposure of rabeprazole at steady state compared to the conventional enteric-coated rabeprazole.
质子泵抑制剂（PPIs）是胃食管反流病（GERD）的一线治疗药物。与传统的非肠溶型 PPI 不同，含有抗酸盐的非肠溶型 PPI 能够通过 PPI 的快速吸收实现更快的酸抑制。YPI-011 是一种新开发的雷贝拉唑与碳酸氢钠（NaHCO）的固定剂量组合。本研究比较了 YPI-011 与传统肠溶型雷贝拉唑（Pariet）的药代动力学（PK）和药效动力学（PD）。
进行了一项随机、开放标签、两治疗、两序列交叉研究，每组有 44 名受试者，分为两个剂量（10 和 20 mg）。他们在第一期随机接受一种测试或参考治疗 7 天，第二期接受另一种治疗。单次和多次给药后采集血样进行 PK 分析。单次和多次给药后进行基础和胃内 pH 监测以进行 PD 分析。
在多剂量后 24 小时间隔内，从基线开始的胃酸综合酸度下降百分比评估的胃酸抑制在两个剂量组的两种治疗方法之间相似。多剂量后稳态时雷贝拉唑的全身暴露在两个剂量组的两种治疗方法之间也相似。测试治疗的达峰时间更快。PPI 的 PK-PD 关系是众所周知的，雷贝拉唑的吸收更快导致酸抑制作用更快。
与传统的肠溶型雷贝拉唑相比，雷贝拉唑与 NaHCO 的固定剂量组合显示出更快的吸收，因此在稳态时具有相似的雷贝拉唑全身暴露水平，但具有更快的胃酸抑制作用。
