CLINICAL TRIAL article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
This article is part of the Research TopicClinical Trials in Drug Metabolism and Transport: 2025View all articles
Pharmacokinetics, mass balance, and metabolism of the novel potassium-competitive acid blocker JP-1366 in healthy Chinese adults following a single oral dose of [14C]JP-1366
Provisionally accepted
Xuemei Liu1
Decheng Deng2
jian Meng3Haitang Hu2Quankun Zhuang1Xue Zhou2
Long Fu2Binke Fan1Xueting Xu1
Qin Huang2*
Xiaoyan Chen3*
Fang Hou1*- 1Phase I Clinical Trial Center, Beijing Gobroad Hospital, Beijing, China
- 2Livzon Pharmaceutical Group Co., Ltd., Zhuhai, China
- 3Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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Introduction: JP-1366 (zastaprazan), a novel potassium-competitive acid blocker (P-CAB), was approved in South Korea in 2024 for treating erosive gastroesophageal reflux disease (GERD). This mass balance study characterized the pharmacokinetics, metabolism, excretion, and safety profile of JP-1366 in humans, supporting its further clinical development in China. Methods: Six healthy Chinese male adults received a single oral dose of 20 mg (100 μCi) [14C]JP-1366 under fasting conditions in this open-label Phase I study. Serial samples of blood, plasma, urine, and feces were collected and analyzed to determine PK parameters, total radioactive recovery, metabolic fate, and excretion routes. Results: JP-1366 was rapidly absorbed, with median Tmax values of 0.875 h observed for both the parent drug and total radioactivity in human plasma. The mean plasma elimination half-life (t1/2) was approximately 28 h for JP-1366-related material. Furthermore, the blood-to-plasma ratio of total radioactivity ranged from 0.561 to 0.645, indicating limited distribution of drug-related material into blood cells. Within 264 h post-dose, 94.3% of the administered radioactive dose was recovered through excretion, predominantly via feces (51.9%) and urine (42.4%). JP-1366 underwent extensive metabolism in vivo, generating 57 metabolites, while the parent drug remained undetectable in excreted samples. The principal metabolic pathways involved oxidations (Phase I) and the following glucuronidation (Phase I/II). JP-1366 exhibited a favorable safety profile, with no serious adverse events reported. Conclusion: JP-1366 exhibited favorable pharmacokinetic properties characterized by rapid absorption, extensive metabolism, and predominant fecal excretion of drug-related material. The principal metabolic pathways involved oxidations and the following glucuronidation.
Keywords: JP-1366, P-CABs, Mass balance study, radioactivity, drug metabolism, pharmacokinetics
Received: 08 Sep 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Liu, Deng, Meng, Hu, Zhuang, Zhou, Fu, Fan, Xu, Huang, Chen and Hou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qin Huang, huangqin01@livzon.cn
Xiaoyan Chen, xychen@simm.ac.cn
Fang Hou, houf@gobroadhealthcare.com
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