The Current State of Biotransformation Science - Industry Survey of In Vitro and In Vivo Practices, Clinical Translation, and Future Trends.

IF 3.5 3区 医学 Q2 CHEMISTRY, MULTIDISCIPLINARY
John P Savaryn, Kevin Coe, Matthew A Cerny, Kevin Colizza, Patricia Moliner, Lloyd King, Bin Ma, Jim Atherton, Adam Auclair, Mark T Cancilla, Marsha Eno, Ulrik Jurva, Qin Yue, Sean Xiaochun Zhu, Elyse Freiberger, Guo Zhong, Ben Barlock, Jonny Nachtigall, Laurent Laboureur, Sandeepraj Pusalkar, Runcong Guo, Michael Niehues, Simon Hauri, Ester Tor Carreras, Christine Maurer, Chandra Prakash, Gary J Jenkins
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Abstract

Embedded within the field of drug metabolism and pharmacokinetics (DMPK), biotransformation is a discipline that studies the origins, disposition, and structural identity of metabolites to provide a comprehensive safety assessment, including the assessment of exposure coverage in toxicological species. Spanning discovery and development, metabolite identification (metID) scientists employ various strategies and tools to address stage-specific questions aimed at guiding the maturation of early chemical matter into drug candidates. During this process, the identity of major (and minor) circulating human metabolites is ascertained to comply with the regulatory requirements such as the Metabolites in Safety Testing (MIST) guidance. Through the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the "Translatability of MetID In Vitro Systems Working Group" was created within the Translational and ADME Sciences Leadership Group. The remit of this group was to objectively determine how accurate commonly employed in vitro systems have been with respect to prediction of circulating human metabolites, both qualitatively and quantitatively. A survey composed of 34 questions was conducted across 26 pharmaceutical companies to obtain a foundational understanding of current metID practices, preclinically and clinically, as well as to provide perspective on how successful these practices have been at predicting circulating human metabolites. The results of this survey are presented as an initial snapshot of current industry-based metID practices, including our perspective on how a harmonized framework for the conduct of in vitro metID studies could be established. Future perspectives from current practices to emerging advances with greater translational capability are also provided.

生物转化科学的现状--体外和体内实践、临床转化和未来趋势的行业调查。
生物转化是药物代谢和药代动力学(DMPK)领域的一门学科,它研究代谢物的来源、处置和结构特性,以提供全面的安全性评估,包括评估毒理学物种的暴露范围。代谢物鉴定(metID)科学家横跨发现和开发两个阶段,采用各种策略和工具来解决特定阶段的问题,旨在指导早期化学物质成熟为候选药物。在此过程中,要确定主要(和次要)循环人体代谢物的身份,以符合法规要求,如安全测试中的代谢物(MIST)指南。通过国际药品开发创新和质量联合会(IQ),在转化和 ADME 科学领导小组内成立了 "MetID 体外系统可转化性工作组"。该工作组的任务是客观确定常用体外系统在定性和定量预测人体循环代谢物方面的准确性。该小组对 26 家制药公司进行了一项包含 34 个问题的调查,以获得对当前临床前和临床中的代谢物检测方法的基本了解,并透视这些方法在预测人体循环代谢物方面的成功程度。本次调查的结果是对当前基于行业的 metID 实践的初步概括,包括我们对如何建立体外 metID 研究统一框架的看法。此外还提供了从当前实践到具有更大转化能力的新兴进展的未来展望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmaceutical Research
Pharmaceutical Research 医学-化学综合
CiteScore
6.60
自引率
5.40%
发文量
276
审稿时长
3.4 months
期刊介绍: Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.
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