利用基于生理的药代动力学模型评估JP-1366和塞来昔布之间的药物相互作用电位。

IF 1.1 Q4 PHARMACOLOGY & PHARMACY
Translational and Clinical Pharmacology Pub Date : 2025-06-01 Epub Date: 2025-06-27 DOI:10.12793/tcp.2025.33.e10
Seung Chan Choi, John Kim, Hyeong-Seok Lim
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引用次数: 0

摘要

Zastaprazan (JP-1366)是一种用于治疗胃肠道反流疾病的新型钾竞争性酸阻滞剂。它是一种口服小分子,可抑制胃H+和K+- atp酶,不同于质子泵抑制剂,作用迅速,对酸分泌有剂量依赖性。塞来昔布是一种选择性环氧化酶2抑制剂,可能会在临床环境和试验中与zastaprazan一起使用。当前基于生理的药代动力学(PBPK)建模研究的目的是预测zastaprazan(肇事者)和塞来昔布(受害者)之间的药物-药物相互作用(DDI)风险。利用实验物理化学性质和计算机预测建立了zastaprazan的人体PBPK模型。该模型采用临床药代动力学(PK)数据进行优化,这些数据来自一项1期研究(方案编号:No. 1)。jp - 1366 - 105)。塞来昔布的PBPK模型是使用先前研究和计算机预测的数据构建的。最终的PBPK模型包括zastaprazan和塞来昔布,用于定量预测人类DDI风险。最终的PBPK模型准确地预测了zastaprazan在人单次给药后的PK谱,也很好地预测了塞来昔布随时间的血浆浓度。以枸橼酸zastaprazan (JAQBO®片剂)20 mg和塞来昔布200 mg为剂量,每24小时口服zastaprazan 7天未增加塞来昔布的曲线下面积(AUC)和最大血药浓度(Cmax), AUC和Cmax的比值均为1,表明zastaprazan对塞来昔布的PK无影响。PBPK建模方法为zastaprazan与塞来昔布之间的dis提供了科学预测,指导了未来的临床开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of drug-drug interaction potentials between JP-1366 and celecoxib using physiologically based pharmacokinetic modeling.

Zastaprazan (JP-1366) is a new potassium-competitive acid blocker being developed for treating gastrointestinal reflux disease. It is an orally administered small molecule that inhibits gastric H+ and K+-ATPases differently from proton pump inhibitors, which act quickly and have dose-dependent effects on acid secretion. Celecoxib, a selective cyclooxygenase 2 inhibitor, will likely be used with zastaprazan in clinical settings and trials. The objective of current physiologically based pharmacokinetic (PBPK) modeling study is to predict drug-drug interaction (DDI) risk between zastaprazan (perpetrator) and celecoxib (victim). A human PBPK model for zastaprazan was built using experimental physicochemical properties and in silico predictions. The model was optimized with clinical pharmacokinetic (PK) data from a phase 1 study (Protocol No. JP-1366-105). The PBPK model for celecoxib was constructed using the data from previous studies and in silico predictions. The final PBPK model encompassing zastaprazan and celecoxib was used to quantitatively predicted DDI risks in humans. The final PBPK models accurately predicted zastaprazan's PK profiles after single dose in human, and it also well predicted plasma celecoxib concentrations over time. At doses of 20 mg of zastaprazan citrate (JAQBO® tablet) and 200 mg of celecoxib, multiple oral doses of zastaprazan every 24 hours for 7 days did not increase celecoxib's area under the curve (AUC) and maximum plasma concentration (Cmax), with ratios of 1 in both AUC and Cmax, indicating no effect of zastaprazan on celecoxib's PK. The PBPK modeling approach provides scientific predictions of DDIs between zastaprazan and celecoxib, guiding future clinical development.

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来源期刊
Translational and Clinical Pharmacology
Translational and Clinical Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.60
自引率
11.10%
发文量
17
期刊介绍: Translational and Clinical Pharmacology (Transl Clin Pharmacol, TCP) is the official journal of the Korean Society for Clinical Pharmacology and Therapeutics (KSCPT). TCP is an interdisciplinary journal devoted to the dissemination of knowledge relating to all aspects of translational and clinical pharmacology. The categories for publication include pharmacokinetics (PK) and drug disposition, drug metabolism, pharmacodynamics (PD), clinical trials and design issues, pharmacogenomics and pharmacogenetics, pharmacometrics, pharmacoepidemiology, pharmacovigilence, and human pharmacology. Studies involving animal models, pharmacological characterization, and clinical trials are appropriate for consideration.
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