{"title":"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。","authors":"Seung Chan Choi, John Kim, Hyeong-Seok Lim","doi":"10.12793/tcp.2025.33.e10","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>in silico</i> 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 <i>in silico</i> 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<sup>®</sup> 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 (C<sub>max</sub>), with ratios of 1 in both AUC and C<sub>max</sub>, 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.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"33 2","pages":"90-99"},"PeriodicalIF":1.1000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12242391/pdf/","citationCount":"0","resultStr":"{\"title\":\"Evaluation of drug-drug interaction potentials between JP-1366 and celecoxib using physiologically based pharmacokinetic modeling.\",\"authors\":\"Seung Chan Choi, John Kim, Hyeong-Seok Lim\",\"doi\":\"10.12793/tcp.2025.33.e10\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>in silico</i> 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 <i>in silico</i> 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<sup>®</sup> 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 (C<sub>max</sub>), with ratios of 1 in both AUC and C<sub>max</sub>, 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.</p>\",\"PeriodicalId\":23288,\"journal\":{\"name\":\"Translational and Clinical Pharmacology\",\"volume\":\"33 2\",\"pages\":\"90-99\"},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12242391/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational and Clinical Pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.12793/tcp.2025.33.e10\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational and Clinical Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.12793/tcp.2025.33.e10","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.