Current opinion in toxicology最新文献_第4页

The universal physiological template—a system to advance medicines 通用生理模板——一个促进药物发展的系统

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.02.002

Eva-Maria Dehne, Uwe Marx

引用次数: 6

Toxicity testing in the era of induced pluripotent stem cells: A perspective regarding the use of patient-specific induced pluripotent stem cell–derived cardiomyocytes for cardiac safety evaluation 诱导多能干细胞时代的毒性测试：使用患者特异性诱导多能干干细胞衍生的心肌细胞进行心脏安全性评估的前景

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.04.001

Li Pang

{"title":"Toxicity testing in the era of induced pluripotent stem cells: A perspective regarding the use of patient-specific induced pluripotent stem cell–derived cardiomyocytes for cardiac safety evaluation","authors":"Li Pang","doi":"10.1016/j.cotox.2020.04.001","DOIUrl":"10.1016/j.cotox.2020.04.001","url":null,"abstract":"<div>The development of human-induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) has opened a new era to address the challenge of improving drug-induced cardiotoxicity prediction. Human iPSC-CMs can be generated from individuals with diverse genetic backgrounds and varying disease status, which provides unprecedented opportunities to assess drug-induced cardiotoxicity at the population level, ultimately, realizing personalized cardiac safety prediction and permitting mechanistic insights into genetic predisposition of drug-induced cardiotoxicity at the molecular and cellular levels. Reviewed herein are successful applications and limitations in using patient-specific iPSC-CMs for cardiac safety evaluation. Future directions for iPSC-CMs are also discussed. The aim of this review is to promote the further development of human iPSC-CM technology to address existing gaps in drug development, improve the prediction of patient susceptibility to therapeutic drugs, and enhance postmarketing surveillance of severe adverse drug reactions.</div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cotox.2020.04.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46492115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

DILIsym: Quantitative systems toxicology impacting drug development DILIsym：影响药物开发的定量系统毒理学

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.06.003

Paul B. Watkins

{"title":"DILIsym: Quantitative systems toxicology impacting drug development","authors":"Paul B. Watkins","doi":"10.1016/j.cotox.2020.06.003","DOIUrl":"10.1016/j.cotox.2020.06.003","url":null,"abstract":"<div>DILIsym®, a quantitative systems toxicology model developed over the last decade by the drug-induced liver injury (DILI)-sim Initiative, has provided novel insights regarding mechanisms underlying drug-induced liver injury and why animal models sometimes fail to accurately assess the liver safety liability of new drug candidates. For example, DILIsym, but not routine preclinical testing, predicted the human hepatotoxicity of the migraine drugs telcagepant and MK3207 that terminated their clinical development. DILIsym also predicted that the next in-class drug, ubrogepant, would be relatively safe for the liver; this prediction was prospectively confirmed in phase-3 clinical trials leading to FDA approval without liver safety warnings. DILIsym also identifies mechanisms underlying liver toxicity, and this information can identify patient-specific risk factors for drug-induced liver injury including drug–drug interactions and certain disease states, improving risk management and pharmacovigilance. DILIsym provides an example of how increased application of quantitative systems toxicology modeling should lead to more efficient development of new drugs.</div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cotox.2020.06.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46220503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Precision medicine in drug safety 精准医学在药品安全中的应用

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.07.003

Daniel F. Carr, Munir Pirmohamed

引用次数: 3

Translational toxicology: An overview 翻译毒理学:综述

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.08.001

Donna L. Mendrick, William B. Mattes

引用次数: 0

In vitro to in vivo translation 体外转体内

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.09.001

William B. Mattes

引用次数: 11

Physiologically based pharmacokinetic modeling: A promising tool for translational research and regulatory toxicology 基于生理学的药代动力学建模：转化研究和调节毒理学的一个有前途的工具

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.03.001

Kiara Fairman , Miao Li , Shruti V. Kabadi , Annie Lumen

{"title":"Physiologically based pharmacokinetic modeling: A promising tool for translational research and regulatory toxicology","authors":"Kiara Fairman , Miao Li , Shruti V. Kabadi , Annie Lumen","doi":"10.1016/j.cotox.2020.03.001","DOIUrl":"10.1016/j.cotox.2020.03.001","url":null,"abstract":"<div>Computational pharmacokinetic modeling methods, such as physiologically based pharmacokinetic (PBPK) modeling, have shown great promise for use in translational research as well as regulatory assessments. PBPK models are assumption-based simplifications of the complex biological system modeled and have high data demands for model parameterization and verification. However, unlike empirical models that rely on multiple observations from a single system, PBPK models uniquely allow for data to be obtained from multiple platforms (in silico, in vitro, and in vivo). Furthermore, these data are integrated by the principles of physiology and pharmacology/toxicology to make predictions in domains with sparse observations. Our article provides an overview of scientific utility of PBPK modeling in translational research and regulatory toxicology using some case examples that highlight the important role of PBPK model-based predictions in contributing to regulatory assessments of diverse types of chemicals, ranging from food and environmental chemicals to drugs intended for use in veterinary and human medicine. At present, collective efforts are ongoing for establishing uniformity, consistency, and transparency within many areas of PBPK modeling, and with continuing advances in the field of computational pharmacokinetic, PBPK modeling has the potential to contribute to reliable alternatives to animal testing in the future.</div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cotox.2020.03.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47967531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Translational imaging in toxicology 毒理学中的翻译成像

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.03.006

Serguei Liachenko

{"title":"Translational imaging in toxicology","authors":"Serguei Liachenko","doi":"10.1016/j.cotox.2020.03.006","DOIUrl":"10.1016/j.cotox.2020.03.006","url":null,"abstract":"<div>In vivo imaging has a potential to bring innovation to translational toxicology for drug discovery. This includes magnetic resonance imaging, positron emission tomography (PET), single photon emission tomography, and computed tomography. The utility of imaging comes from its capacity to provide minimally invasive biomarkers for safety profiling and decision-making in drug discovery. Nonspecific biomarkers, such as magnetic resonance imaging relaxometry, computed tomography density, or PET 18F-fluoro-2-deoxy-d-glucose are better suited for preclinical general toxicology and clinical monitoring, while specific ones, such as most of PET and single photon emission tomography ligands, are better suited to clarify mechanisms of toxicity or unwanted target engagement. However, the use of these biomarkers is sporadic and governed by scientific interest and availability rather than its utility. A systematic approach is needed to qualify these biomarkers with regulatory authorities so translational imaging could be incorporated into drug development and its unique potential translated into safer and cheaper medicines.</div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cotox.2020.03.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43608267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Quantitative structure–toxicity relationships in translational toxicology 转化毒理学中的定量结构-毒性关系

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.04.002

Svetoslav Slavov, Richard D. Beger

引用次数: 4

Considerations in the extrapolation of drug toxicity between humans and dogs 人犬间药物毒性外推的考虑

IF 4.6

Current opinion in toxicology Pub Date : 2020-10-01 DOI: 10.1016/j.cotox.2020.05.005

Marilyn N. Martinez , Jonathan P. Mochel , Devendra Pade

引用次数: 3