Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
Aliment Pharmacol Ther. 2019 Oct;50(7):751-759. doi: 10.1111/apt.15438. Epub 2019 Aug 22.
Tegoprazan (CJ-12420) is a potassium-competitive acid blocker (P-CAB) with therapeutic potential for gastro-oesophageal reflux disease (GERD) by reversibly suppressing gastric H /K -ATPase.
To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of tegoprazan METHODS: A phase I, randomised, double-blind and placebo-controlled clinical trial was conducted in 56 healthy male subjects without Helicobacter pylori infection. In the single ascending dose study, 50, 100, 200 and 400 mg tegoprazan were administered to 32 subjects. In the multiple ascending dose study, 100 and 200 mg tegoprazan were administered every 24 hours to each of the eight subjects for 7 days. In the comparative pharmacodynamics study, 40 mg esomeprazole was administered to eight subjects every 24 hours for 7 days. The assessment included safety, tolerability, pharmacodynamics through monitoring of 24-hour gastric pH and pharmacokinetics of tegoprazan in plasma and urine.
Tegoprazan was generally well tolerated. Most adverse events reported in the study were mild in intensity and resolved without any sequelae. Exposure to tegoprazan increased in a dose-proportional manner. Multiple dosing with tegoprazan showed no accumulation in plasma on day 7. The pharmacodynamic analysis revealed that tegoprazan showed rapid, dose-dependent gastric acid suppression.
Tegoprazan was well tolerated and showed rapid and potent gastric acid suppression. This supports the further development of tegoprazan as a treatment for acid-related disorders.
替戈拉赞（CJ-12420）是一种钾离子竞争型酸阻滞剂（P-CAB），通过可逆抑制胃 H+/K+-ATP 酶，具有治疗胃食管反流病（GERD）的潜力。
研究替戈拉赞的安全性、耐受性、药代动力学和药效学。
一项在 56 名未感染幽门螺杆菌的健康男性受试者中进行的 I 期、随机、双盲、安慰剂对照临床试验。在单次递增剂量研究中，32 名受试者接受了 50、100、200 和 400mg 替戈拉赞的治疗。在多次递增剂量研究中，8 名受试者每天每 24 小时分别接受 100 和 200mg 替戈拉赞的治疗，持续 7 天。在比较药效学研究中，8 名受试者每天每 24 小时接受 40mg 艾司奥美拉唑治疗，持续 7 天。评估包括安全性、耐受性、通过监测 24 小时胃 pH 值评估的药效学以及替戈拉赞在血浆和尿液中的药代动力学。
替戈拉赞总体上具有良好的耐受性。研究中报告的大多数不良事件为轻度，且无任何后遗症自行缓解。替戈拉赞的暴露量呈剂量依赖性增加。替戈拉赞在第 7 天多次给药时在血浆中无蓄积。药效学分析显示，替戈拉赞可迅速、剂量依赖性地抑制胃酸。
替戈拉赞具有良好的耐受性，并表现出快速而强效的胃酸抑制作用。这支持进一步开发替戈拉赞作为酸相关疾病的治疗药物。
