{"title":"使用14c放射性标记技术的新型钾竞争酸阻滞剂替哥拉赞的人体质量平衡和代谢物谱。","authors":"Yicong Bian, Jinjie Yuan, Sheng Ma, Jiang Nan, Zheming Gu, Hao Feng, Zhenwen Yu, Zhenteng Liu, Fang Xie, Yinghui Wang, Chengxin Liu, Hua Zhang, Liyan Miao","doi":"10.1080/17425255.2025.2505637","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Tegoprazan (LXI-15028), a novel potassium-competitive acid blocker, has shown great efficacy in treating acid-related disorders. However, its metabolic and excretion characteristics are not fully understood.</p><p><strong>Research design and methods: </strong>A single oral dose of 50 mg/150 μCi [<sup>14</sup>C]tegoprazan was administered to six healthy subjects. Blood, urine and fecal samples were collected and measured for total radioactivity (TRA), tegoprazan and metabolites. Its safety was also assessed.</p><p><strong>Results: </strong>The maximum concentrations (C<sub>max</sub>) of tegoprazan and TRA in plasma were 634 ng/mL and 990 ng eq./mL, respectively, at 0.5 h post dose. Tegoprazan and its N-demethylation metabolite (M1) were the major drug-related compounds in plasma, accounting for 34.84% and 40.10% of TRA, respectively. The half-life (t<sub>1/2</sub>) of TRA (8.72 h) was longer than that of tegoprazan (4.33 h) in plasma, indicating slower metabolite elimination. Tegoprazan was excreted through both the urine (50.51 ± 3.35%) and feces (47.26 ± 3.06%). The main metabolic pathways of tegoprazan are demethylation, oxidation, glucuronidation and sulfation. There were no serious adverse events observed in this study.</p><p><strong>Conclusions: </strong>Tegoprazan is widely metabolized and excreted completely in humans. Tegoprazan and M1 were the primary compounds present in the circulation.</p><p><strong>Clinical trial registration: </strong>www.clinicaltrials.gov identifier is NCT05883306.</p>","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"897-907"},"PeriodicalIF":0.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mass balance and metabolite profiles in humans of tegoprazan, a novel potassium-competitive acid blocker, using <sup>14</sup>C-radiolabelled techniques.\",\"authors\":\"Yicong Bian, Jinjie Yuan, Sheng Ma, Jiang Nan, Zheming Gu, Hao Feng, Zhenwen Yu, Zhenteng Liu, Fang Xie, Yinghui Wang, Chengxin Liu, Hua Zhang, Liyan Miao\",\"doi\":\"10.1080/17425255.2025.2505637\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Tegoprazan (LXI-15028), a novel potassium-competitive acid blocker, has shown great efficacy in treating acid-related disorders. However, its metabolic and excretion characteristics are not fully understood.</p><p><strong>Research design and methods: </strong>A single oral dose of 50 mg/150 μCi [<sup>14</sup>C]tegoprazan was administered to six healthy subjects. Blood, urine and fecal samples were collected and measured for total radioactivity (TRA), tegoprazan and metabolites. Its safety was also assessed.</p><p><strong>Results: </strong>The maximum concentrations (C<sub>max</sub>) of tegoprazan and TRA in plasma were 634 ng/mL and 990 ng eq./mL, respectively, at 0.5 h post dose. Tegoprazan and its N-demethylation metabolite (M1) were the major drug-related compounds in plasma, accounting for 34.84% and 40.10% of TRA, respectively. The half-life (t<sub>1/2</sub>) of TRA (8.72 h) was longer than that of tegoprazan (4.33 h) in plasma, indicating slower metabolite elimination. Tegoprazan was excreted through both the urine (50.51 ± 3.35%) and feces (47.26 ± 3.06%). The main metabolic pathways of tegoprazan are demethylation, oxidation, glucuronidation and sulfation. There were no serious adverse events observed in this study.</p><p><strong>Conclusions: </strong>Tegoprazan is widely metabolized and excreted completely in humans. Tegoprazan and M1 were the primary compounds present in the circulation.</p><p><strong>Clinical trial registration: </strong>www.clinicaltrials.gov identifier is NCT05883306.</p>\",\"PeriodicalId\":94005,\"journal\":{\"name\":\"Expert opinion on drug metabolism & toxicology\",\"volume\":\" \",\"pages\":\"897-907\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert opinion on drug metabolism & toxicology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/17425255.2025.2505637\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on drug metabolism & toxicology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/17425255.2025.2505637","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/13 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Mass balance and metabolite profiles in humans of tegoprazan, a novel potassium-competitive acid blocker, using 14C-radiolabelled techniques.
Background: Tegoprazan (LXI-15028), a novel potassium-competitive acid blocker, has shown great efficacy in treating acid-related disorders. However, its metabolic and excretion characteristics are not fully understood.
Research design and methods: A single oral dose of 50 mg/150 μCi [14C]tegoprazan was administered to six healthy subjects. Blood, urine and fecal samples were collected and measured for total radioactivity (TRA), tegoprazan and metabolites. Its safety was also assessed.
Results: The maximum concentrations (Cmax) of tegoprazan and TRA in plasma were 634 ng/mL and 990 ng eq./mL, respectively, at 0.5 h post dose. Tegoprazan and its N-demethylation metabolite (M1) were the major drug-related compounds in plasma, accounting for 34.84% and 40.10% of TRA, respectively. The half-life (t1/2) of TRA (8.72 h) was longer than that of tegoprazan (4.33 h) in plasma, indicating slower metabolite elimination. Tegoprazan was excreted through both the urine (50.51 ± 3.35%) and feces (47.26 ± 3.06%). The main metabolic pathways of tegoprazan are demethylation, oxidation, glucuronidation and sulfation. There were no serious adverse events observed in this study.
Conclusions: Tegoprazan is widely metabolized and excreted completely in humans. Tegoprazan and M1 were the primary compounds present in the circulation.
Clinical trial registration: www.clinicaltrials.gov identifier is NCT05883306.
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