跨越鸿沟:如何进行噬菌体剂量的转化药代动力学-药效学建模。

IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacology & Therapeutics Pub Date : 2024-09-23 DOI:10.1002/cpt.3426
Gauri G Rao, Quentin Vallé, Ramya Mahadevan, Rajnikant Sharma, Jeremy J Barr, Daria Van Tyne
{"title":"跨越鸿沟:如何进行噬菌体剂量的转化药代动力学-药效学建模。","authors":"Gauri G Rao, Quentin Vallé, Ramya Mahadevan, Rajnikant Sharma, Jeremy J Barr, Daria Van Tyne","doi":"10.1002/cpt.3426","DOIUrl":null,"url":null,"abstract":"<p><p>Effectively treating multidrug-resistant bacterial infections remains challenging due to the limited drug development pipeline and a scarcity of novel agents effective against these highly resistant pathogens. Bacteriophages (phages) are a potential addition to the antimicrobial treatment arsenal. Though, phages are currently being tested in clinical trials for antibiotic-resistant infections, phages lack a fundamental understanding of optimal dosing in humans. Rationally designed preclinical studies using in vitro and in vivo infection models, allow us to assess clinically relevant phage +/- antibiotic exposure (pharmacokinetics), the resulting treatment impact on the infecting pathogen (pharmacodynamics) and host immune response (immunodynamics). A mechanistic modeling framework allows us to integrate this knowledge gained from preclinical studies to develop predictive models. We reviewed recently published mathematical models based on in vitro and/or in vivo data that evaluate the effects of varying bacterial or phage densities, phage characteristics (burst size, adsorption rate), phage pharmacokinetics, phage-antibiotic combinations and host immune responses. In our review, we analyzed study designs and the data used to inform the development of these mechanistic models. Insights gained from model-based simulations were reviewed as they help identify crucial phage parameters for determining effective phage dosing. These efforts contribute to bridging the gap between phage therapy research and its clinical translation.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Crossing the Chasm: How to Approach Translational Pharmacokinetic-Pharmacodynamic Modeling of Phage Dosing.\",\"authors\":\"Gauri G Rao, Quentin Vallé, Ramya Mahadevan, Rajnikant Sharma, Jeremy J Barr, Daria Van Tyne\",\"doi\":\"10.1002/cpt.3426\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Effectively treating multidrug-resistant bacterial infections remains challenging due to the limited drug development pipeline and a scarcity of novel agents effective against these highly resistant pathogens. Bacteriophages (phages) are a potential addition to the antimicrobial treatment arsenal. Though, phages are currently being tested in clinical trials for antibiotic-resistant infections, phages lack a fundamental understanding of optimal dosing in humans. Rationally designed preclinical studies using in vitro and in vivo infection models, allow us to assess clinically relevant phage +/- antibiotic exposure (pharmacokinetics), the resulting treatment impact on the infecting pathogen (pharmacodynamics) and host immune response (immunodynamics). A mechanistic modeling framework allows us to integrate this knowledge gained from preclinical studies to develop predictive models. We reviewed recently published mathematical models based on in vitro and/or in vivo data that evaluate the effects of varying bacterial or phage densities, phage characteristics (burst size, adsorption rate), phage pharmacokinetics, phage-antibiotic combinations and host immune responses. In our review, we analyzed study designs and the data used to inform the development of these mechanistic models. Insights gained from model-based simulations were reviewed as they help identify crucial phage parameters for determining effective phage dosing. These efforts contribute to bridging the gap between phage therapy research and its clinical translation.</p>\",\"PeriodicalId\":153,\"journal\":{\"name\":\"Clinical Pharmacology & Therapeutics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":6.3000,\"publicationDate\":\"2024-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Pharmacology & Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/cpt.3426\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Pharmacology & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cpt.3426","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

由于药物开发渠道有限,而且缺乏能有效对付这些高度耐药病原体的新型制剂,因此有效治疗耐多药细菌感染仍具有挑战性。噬菌体(噬菌体)是抗菌治疗药物库中的潜在新成员。虽然噬菌体目前正在抗生素耐药性感染的临床试验中进行测试,但人们对噬菌体在人体中的最佳剂量缺乏基本了解。通过使用体外和体内感染模型进行合理设计的临床前研究,我们可以评估与临床相关的噬菌体+/-抗生素暴露(药代动力学)、治疗对感染病原体的影响(药效学)和宿主免疫反应(免疫动力学)。机理建模框架使我们能够整合从临床前研究中获得的这些知识来开发预测模型。我们回顾了最近发表的基于体外和/或体内数据的数学模型,这些模型评估了不同细菌或噬菌体密度、噬菌体特性(爆发大小、吸附率)、噬菌体药代动力学、噬菌体-抗生素组合和宿主免疫反应的影响。在我们的综述中,我们分析了研究设计和用于指导这些机理模型开发的数据。我们还回顾了从基于模型的模拟中获得的启示,因为这些启示有助于确定噬菌体的关键参数,从而确定噬菌体的有效剂量。这些努力有助于缩小噬菌体疗法研究与临床转化之间的差距。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Crossing the Chasm: How to Approach Translational Pharmacokinetic-Pharmacodynamic Modeling of Phage Dosing.

Effectively treating multidrug-resistant bacterial infections remains challenging due to the limited drug development pipeline and a scarcity of novel agents effective against these highly resistant pathogens. Bacteriophages (phages) are a potential addition to the antimicrobial treatment arsenal. Though, phages are currently being tested in clinical trials for antibiotic-resistant infections, phages lack a fundamental understanding of optimal dosing in humans. Rationally designed preclinical studies using in vitro and in vivo infection models, allow us to assess clinically relevant phage +/- antibiotic exposure (pharmacokinetics), the resulting treatment impact on the infecting pathogen (pharmacodynamics) and host immune response (immunodynamics). A mechanistic modeling framework allows us to integrate this knowledge gained from preclinical studies to develop predictive models. We reviewed recently published mathematical models based on in vitro and/or in vivo data that evaluate the effects of varying bacterial or phage densities, phage characteristics (burst size, adsorption rate), phage pharmacokinetics, phage-antibiotic combinations and host immune responses. In our review, we analyzed study designs and the data used to inform the development of these mechanistic models. Insights gained from model-based simulations were reviewed as they help identify crucial phage parameters for determining effective phage dosing. These efforts contribute to bridging the gap between phage therapy research and its clinical translation.

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
CiteScore
12.70
自引率
7.50%
发文量
290
审稿时长
2 months
期刊介绍: Clinical Pharmacology & Therapeutics (CPT) is the authoritative cross-disciplinary journal in experimental and clinical medicine devoted to publishing advances in the nature, action, efficacy, and evaluation of therapeutics. CPT welcomes original Articles in the emerging areas of translational, predictive and personalized medicine; new therapeutic modalities including gene and cell therapies; pharmacogenomics, proteomics and metabolomics; bioinformation and applied systems biology complementing areas of pharmacokinetics and pharmacodynamics, human investigation and clinical trials, pharmacovigilence, pharmacoepidemiology, pharmacometrics, and population pharmacology.
期刊最新文献
Cerebral Ischemia Protection After Aneurysmal Subarachnoid Hemorrhage: CSF Nimodipine Levels After Intravenous Versus Oral Nimodipine Administration. Contemporary Use of β-Blockers in Heart Failure Patients With and Without Atrial Fibrillation: A Nationwide Database Analysis. Correction to Effectively Leveraging RWD for External Controls: A Systematic Literature Review of Regulatory and HTA Decisions. Infection Risk Associated with High-Efficacy Disease-Modifying Agents in Multiple Sclerosis: A Retrospective Cohort Study. In This Issue
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1