Yujing Du, Lixiu Yu, Bin Deng, Qinying Li, Junrui Hu, Linjie Li, Yusen Xu, Liangwei Song, Fang Xie, Yinghui Wang, Yuhao Chen, Chengxin Liu, Xuejia Zhai, Yongning Lu
{"title":"中国健康受试者特戈普拉赞与克拉霉素、阿莫西林和铋剂复方制剂之间的药代动力学相互作用：一项开放标签、单中心、多剂量、自我控制的 I 期试验","authors":"Yujing Du, Lixiu Yu, Bin Deng, Qinying Li, Junrui Hu, Linjie Li, Yusen Xu, Liangwei Song, Fang Xie, Yinghui Wang, Yuhao Chen, Chengxin Liu, Xuejia Zhai, Yongning Lu","doi":"10.1007/s40261-024-01359-x","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating <i>Helicobacter pylori</i>. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14–20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21–27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (<i>C</i><sub>max,ss</sub>) and area under the plasma concentration–time curve over the dosing interval (AUC<sub>τ</sub>) at steady state were 195.93% (175.52–218.71%) and 287.54% (263.28–314.04%) for tegoprazan and 423.23% (382.57–468.22%) and 385.61% (354.62–419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of <i>C</i><sub>max,ss</sub> and AUC<sub>τ</sub> were 83.69% (77.44–90.45%) and 110.30% (102.74–118.41%) for clarithromycin, 126.25% (114.73–138.93%) and 146.94% (135.33–159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73–82.60%) and 94.34% (87.94–101.20%) for amoxicillin, and 158.43% (125.43–200.11%) and 183.63% (156.42–215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability.</p><h3 data-test=\"abstract-sub-heading\">Clinical Trials Registration</h3><p>CTR20230643.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"93 1","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial\",\"authors\":\"Yujing Du, Lixiu Yu, Bin Deng, Qinying Li, Junrui Hu, Linjie Li, Yusen Xu, Liangwei Song, Fang Xie, Yinghui Wang, Yuhao Chen, Chengxin Liu, Xuejia Zhai, Yongning Lu\",\"doi\":\"10.1007/s40261-024-01359-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background</h3><p>Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating <i>Helicobacter pylori</i>. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14–20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21–27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (<i>C</i><sub>max,ss</sub>) and area under the plasma concentration–time curve over the dosing interval (AUC<sub>τ</sub>) at steady state were 195.93% (175.52–218.71%) and 287.54% (263.28–314.04%) for tegoprazan and 423.23% (382.57–468.22%) and 385.61% (354.62–419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of <i>C</i><sub>max,ss</sub> and AUC<sub>τ</sub> were 83.69% (77.44–90.45%) and 110.30% (102.74–118.41%) for clarithromycin, 126.25% (114.73–138.93%) and 146.94% (135.33–159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73–82.60%) and 94.34% (87.94–101.20%) for amoxicillin, and 158.43% (125.43–200.11%) and 183.63% (156.42–215.58%) for bismuth, respectively. All reported adverse events were mild. 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The coadministration exhibited favorable safety and tolerability.</p><h3 data-test=\\\"abstract-sub-heading\\\">Clinical Trials Registration</h3><p>CTR20230643.</p>\",\"PeriodicalId\":10402,\"journal\":{\"name\":\"Clinical Drug Investigation\",\"volume\":\"93 1\",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-04-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Drug Investigation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40261-024-01359-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Drug Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40261-024-01359-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial
Background
Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects.
Methods
An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14–20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21–27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period.
Results
The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration–time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52–218.71%) and 287.54% (263.28–314.04%) for tegoprazan and 423.23% (382.57–468.22%) and 385.61% (354.62–419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44–90.45%) and 110.30% (102.74–118.41%) for clarithromycin, 126.25% (114.73–138.93%) and 146.94% (135.33–159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73–82.60%) and 94.34% (87.94–101.20%) for amoxicillin, and 158.43% (125.43–200.11%) and 183.63% (156.42–215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages.
Conclusion
The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability.
期刊介绍：
Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes:
-Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs.
-Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice.
-Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed.
-Studies focusing on the application of drug delivery technology in healthcare.
-Short communications and case study reports that meet the above criteria will also be considered.
Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.
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