Hwang Jun Gi, Yoo Hyounggyoon, Lee Ji Won, Song Geun Seog, Lee SeungHwan, Kim Min-Gul
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea.
Clinical Development Division, CJ HealthCare Corp., Seoul 04551, Republic of Korea.
Transl Clin Pharmacol. 2019 Jun;27(2):80-85. doi: 10.12793/tcp.2019.27.2.80. Epub 2019 Jun 28.
Proton-pump inhibitors (PPIs) are effectively used to treat acid-related diseases, including gastroesophageal reflux disease (GERD); however, many unmet medical needs still exist. As a new treatment option, potassium-competitive acid blockers (P-CABs), such as tegoprazan, have been developed. This study was performed to compare the pharmacokinetics (PKs) between two formulations (test and reference drugs) of tegoprazan 100 mg tablets. A randomized, single oral dose, two-treatment, two-period, two-sequence study was conducted with 12 healthy subjects. Each subject received the test drug or reference drug in the first period and the alternative treatment in the second period. For PK evaluation, blood samples were collected up to 48 hours post-dose in each period. The plasma concentrations of tegoprazan and its active metabolite (M1) were measured by liquid chromatography-tandem mass spectrometry. PK parameters, including maximum plasma concentration (C) and area under the concentration-time curve from zero to the last measurable time (AUC), were estimated using a non-compartmental method. The plasma concentration-time profiles of the two formulations were comparable. The geometric mean ratios [90% confidence intervals (CIs)] of the test drug to the reference drug for C and AUC were 0.98 (0.85-1.12) and 1.03 (0.93-1.13), respectively. The corresponding values of M1 were 0.99 (0.89-1.11) and 1.01 (0.93-1.09), respectively. The two formulations of tegoprazan exhibited comparable PK profiles, fulfilling the regulatory criteria for bioequivalence.
质子泵抑制剂（PPIs）被有效地用于治疗与酸相关的疾病，包括胃食管反流病（GERD）；然而，许多未满足的医疗需求仍然存在。作为一种新的治疗选择，已开发出钾竞争性酸阻滞剂（P-CABs），如替戈拉赞。本研究旨在比较替戈拉赞100mg片剂两种制剂（试验药物和参比药物）之间的药代动力学（PKs）。对12名健康受试者进行了一项随机、单次口服给药、双治疗、双周期、双序列研究。每个受试者在第一周期接受试验药物或参比药物，在第二周期接受替代治疗。为进行PK评估，在每个周期给药后长达48小时采集血样。通过液相色谱-串联质谱法测定替戈拉赞及其活性代谢物（M1）的血浆浓度。使用非房室方法估算PK参数，包括最大血浆浓度（C）和从零至最后可测量时间的浓度-时间曲线下面积（AUC）。两种制剂的血浆浓度-时间曲线具有可比性。试验药物与参比药物的C和AUC的几何平均比值[90%置信区间（CIs）]分别为0.98（0.85-1.12）和1.03（0.93-1.13）。M1的相应值分别为0.99（0.89-1.11）和1.01（0.93-1.09）。替戈拉赞的两种制剂表现出可比的PK特征，符合生物等效性的监管标准。
