抗病毒药物氟噻嗪酮在大鼠和兔子体内的药代动力学、组织分布、生物利用度和排泄。

IF 2.1 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Antibiotics Pub Date : 2024-03-15 DOI:10.1038/s41429-024-00719-1

Mark V. Savitskii, Natalia E. Moskaleva, Alex Brito, Pavel A. Markin, Nailya A. Zigangirova, Anna V. Soloveva, Anna B. Sheremet, Natalia E. Bondareva, Nadezhda L. Lubenec, Franco Tagliaro, Vadim V. Tarasov, Kristina A. Tatzhikova, Svetlana A. Appolonova

{"title":"抗病毒药物氟噻嗪酮在大鼠和兔子体内的药代动力学、组织分布、生物利用度和排泄。","authors":"Mark V. Savitskii, Natalia E. Moskaleva, Alex Brito, Pavel A. Markin, Nailya A. Zigangirova, Anna V. Soloveva, Anna B. Sheremet, Natalia E. Bondareva, Nadezhda L. Lubenec, Franco Tagliaro, Vadim V. Tarasov, Kristina A. Tatzhikova, Svetlana A. Appolonova","doi":"10.1038/s41429-024-00719-1","DOIUrl":null,"url":null,"abstract":"Growing antimicrobial resistance has accelerated the development of anti-virulence drugs to suppress bacterial toxicity without affecting cell viability. Fluorothiazinon (FT), an anti-virulence, type three secretion system and flagella motility inhibitor which has shown promise to suppress drug-resistant pathogens having the potential to enhance the efficacy of commonly prescribed antibiotics when used in combination. In this study we characterized the pharmacokinetics, tissue distribution, bioavailability and excretion of FT in rats and rabbits. FT presented a dose-proportional linear increase in the blood of rats. Tissue distribution profiling confirmed that FT distributes to all organs being substantially higher than in the blood of rats. The bioavailability of FT was higher when administered with starch than with water implying FT should be ideally dosed with food. FT was primarily excreted in the feces in rats and rabbits while negligible amounts are recovered from the urine.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 6","pages":"382-388"},"PeriodicalIF":2.1000,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics, tissue distribution, bioavailability and excretion of the anti-virulence drug Fluorothiazinon in rats and rabbits\",\"authors\":\"Mark V. Savitskii, Natalia E. Moskaleva, Alex Brito, Pavel A. Markin, Nailya A. Zigangirova, Anna V. Soloveva, Anna B. Sheremet, Natalia E. Bondareva, Nadezhda L. Lubenec, Franco Tagliaro, Vadim V. Tarasov, Kristina A. Tatzhikova, Svetlana A. Appolonova\",\"doi\":\"10.1038/s41429-024-00719-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Growing antimicrobial resistance has accelerated the development of anti-virulence drugs to suppress bacterial toxicity without affecting cell viability. Fluorothiazinon (FT), an anti-virulence, type three secretion system and flagella motility inhibitor which has shown promise to suppress drug-resistant pathogens having the potential to enhance the efficacy of commonly prescribed antibiotics when used in combination. In this study we characterized the pharmacokinetics, tissue distribution, bioavailability and excretion of FT in rats and rabbits. FT presented a dose-proportional linear increase in the blood of rats. Tissue distribution profiling confirmed that FT distributes to all organs being substantially higher than in the blood of rats. The bioavailability of FT was higher when administered with starch than with water implying FT should be ideally dosed with food. FT was primarily excreted in the feces in rats and rabbits while negligible amounts are recovered from the urine.\",\"PeriodicalId\":54884,\"journal\":{\"name\":\"Journal of Antibiotics\",\"volume\":\"77 6\",\"pages\":\"382-388\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Antibiotics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41429-024-00719-1\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Antibiotics","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41429-024-00719-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

抗菌药耐药性的不断增加加速了抗病毒药物的开发，以在不影响细胞活力的情况下抑制细菌毒性。氟噻嗪侬（FT）是一种抗病毒药、三型分泌系统和鞭毛运动抑制剂，有望抑制耐药性病原体，在联合使用时有可能提高常用抗生素的疗效。在这项研究中，我们研究了 FT 在大鼠和兔子体内的药代动力学、组织分布、生物利用度和排泄情况。FT 在大鼠血液中呈剂量比例线性增加。组织分布剖析证实，FT 在所有器官中的分布均远高于在大鼠血液中的分布。与淀粉一起给药时，FT 的生物利用率高于与水一起给药时，这意味着 FT 最好与食物一起给药。大鼠和家兔的 FT 主要通过粪便排泄，而从尿液中回收的量微乎其微。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Pharmacokinetics, tissue distribution, bioavailability and excretion of the anti-virulence drug Fluorothiazinon in rats and rabbits

查看原文本刊更多论文

Pharmacokinetics, tissue distribution, bioavailability and excretion of the anti-virulence drug Fluorothiazinon in rats and rabbits

Growing antimicrobial resistance has accelerated the development of anti-virulence drugs to suppress bacterial toxicity without affecting cell viability. Fluorothiazinon (FT), an anti-virulence, type three secretion system and flagella motility inhibitor which has shown promise to suppress drug-resistant pathogens having the potential to enhance the efficacy of commonly prescribed antibiotics when used in combination. In this study we characterized the pharmacokinetics, tissue distribution, bioavailability and excretion of FT in rats and rabbits. FT presented a dose-proportional linear increase in the blood of rats. Tissue distribution profiling confirmed that FT distributes to all organs being substantially higher than in the blood of rats. The bioavailability of FT was higher when administered with starch than with water implying FT should be ideally dosed with food. FT was primarily excreted in the feces in rats and rabbits while negligible amounts are recovered from the urine.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Journal of Antibiotics 医学-免疫学

CiteScore

6.60

自引率

3.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Antibiotics seeks to promote research on antibiotics and related types of biologically active substances and publishes Articles, Review Articles, Brief Communication, Correspondence and other specially commissioned reports. The Journal of Antibiotics accepts papers on biochemical, chemical, microbiological and pharmacological studies. However, studies regarding human therapy do not fall under the journal’s scope. Contributions regarding recently discovered antibiotics and biologically active microbial products are particularly encouraged. Topics of particular interest within the journal''s scope include, but are not limited to, those listed below: Discovery of new antibiotics and related types of biologically active substances Production, isolation, characterization, structural elucidation, chemical synthesis and derivatization, biological activities, mechanisms of action, and structure-activity relationships of antibiotics and related types of biologically active substances Biosynthesis, bioconversion, taxonomy and genetic studies on producing microorganisms, as well as improvement of production of antibiotics and related types of biologically active substances Novel physical, chemical, biochemical, microbiological or pharmacological methods for detection, assay, determination, structural elucidation and evaluation of antibiotics and related types of biologically active substances Newly found properties, mechanisms of action and resistance-development of antibiotics and related types of biologically active substances.