Department of Pharmacology and Clinical Pharmacology, Pharmacogenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Korea.
J Clin Pharmacol. 2021 Jul;61(7):913-922. doi: 10.1002/jcph.1805. Epub 2021 Jan 12.
This clinical trial was conducted to evaluate the pharmacokinetics and pharmacodynamics of tegoprazan when coadministered with amoxicillin/clarithromycin in healthy subjects. Cohort 1 was an open-label, randomized multiple-dose study to evaluate the mutual interaction of tegoprazan and amoxicillin/clarithromycin on the disposition of 3 tested drugs including tegoprazan M1 metabolite and 14-hydroxyclarithromycin (14-OH-clarithromycin). Cohort 2 was an open-label, randomized, active-controlled, parallel multiple-dose study to compare the intragastric pH profile after multiple oral doses of 50 or 100 mg tegoprazan coadministered with amoxicillin/clarithromycin 1000/500 mg for 7 days and pantoprazole-based triple therapy as the comparator arm. The coadministration of tegoprazan with amoxicillin/clarithromycin increased C (2.2-fold) and AUC (2.7-fold) of tegoprazan and M1 (2.1- and 2.2-fold for C and AUC , respectively) compared with administration of tegoprazan alone. The C and AUC of 14-OH-clarithromycin increased by 1.7- and 1.8-fold, respectively; the disposition of amoxicillin and clarithromycin were not significantly changed. On days 1 and 7 of treatment, tegoprazan-based therapies (both 50- and 100-mg therapies) maintained pH above 6 for more than 88% of the 24-hour period, which was significantly longer compared with pantoprazole-based therapy. Tegoprazan either alone or in combination with amoxicillin/clarithromycin was well tolerated in healthy subjects. In conclusion, the exposure of tegoprazan was increased after coadministration of amoxicillin/clarithromycin, which led to increase pharmacodynamic response measured by intragastric pH compared with tegoprazan alone. Therefore, tegoprazan-based triple therapy would be effective therapeutic regimen to manage intragastric pH in terms of gastric or duodenal ulcers healing, treatment of gastroesophageal reflux disease, and Helicobacter pylori eradication.
这项临床试验旨在评估替戈拉赞与阿莫西林/克拉维酸合用在健康受试者中的药代动力学和药效学。队列 1 为开放标签、随机、多剂量研究，用于评估替戈拉赞和阿莫西林/克拉维酸对 3 种受试药物（包括替戈拉赞 M1 代谢物和 14-羟基克拉霉素（14-OH-克拉霉素））处置的相互作用。队列 2 为开放标签、随机、阳性对照、平行多剂量研究，比较了替戈拉赞 50 或 100mg 与阿莫西林/克拉维酸 1000/500mg 合用 7 天与泮托拉唑三联疗法作为对照臂时多次口服给药后的胃内 pH 谱。与单独给予替戈拉赞相比，替戈拉赞与阿莫西林/克拉维酸合用使替戈拉赞（C：2.2 倍；AUC：2.7 倍）和 M1（C：2.1-2.2 倍；AUC：2.1-2.2 倍）的 C 和 AUC 增加。14-OH-克拉霉素的 C 和 AUC 分别增加 1.7 倍和 1.8 倍；阿莫西林和克拉霉素的处置没有显著变化。在治疗的第 1 天和第 7 天，替戈拉赞治疗（50mg 和 100mg 治疗）在 24 小时内使 pH 值保持在 6 以上的时间超过 88%，与泮托拉唑治疗相比显著延长。替戈拉赞单独或与阿莫西林/克拉维酸合用在健康受试者中耐受良好。总之，替戈拉赞与阿莫西林/克拉维酸合用后，暴露量增加，与单独使用替戈拉赞相比，胃内 pH 值的药效反应增加。因此，替戈拉赞三联疗法可能是一种有效的治疗方案，可用于治疗胃或十二指肠溃疡愈合、治疗胃食管反流病和根除幽门螺杆菌，以控制胃内 pH 值。
