Scaling factors to inform in vitro-in vivo extrapolation from preclinical and livestock animals: state of the field and recommendations for development of missing data.

IF 3.4 2区 医学 Q2 PHARMACOLOGY & PHARMACY
Austin A Zimmer, Abby C Collier
{"title":"Scaling factors to inform <i>in vitro</i>-<i>in vivo</i> extrapolation from preclinical and livestock animals: state of the field and recommendations for development of missing data.","authors":"Austin A Zimmer, Abby C Collier","doi":"10.1080/03602532.2025.2462527","DOIUrl":null,"url":null,"abstract":"<p><p>The use of <i>in-vitro</i>-<i>in-vivo</i> physiologically based pharmacokinetic (IVIVE-PBPK) modeling approaches assists for prediction of first-in animal or human trials. These approaches are underpinned by the scaling factors: microsomal protein per gram (MPPG) and cytosolic protein per gram (CPPG). In addition, IVIVE-PBPK has significant application in the reduction and refinement of live animal models in research. While human scaling factors are well-defined, many preclinical and livestock species remain poorly elucidated or uncharacterized. The MPPG parameter for liver (MPPGL) is the best characterized across all species and is well-defined for mouse, rat, and dog models. The MPPG parameters for Kidney (MPPGK) and intestine (MPPGI), are however; relatively indefinite for most species. Similarly, CPPG scaling factors for liver, kidney, and intestine (CPPGL/CPPGK/CPPGI) are generally sparse in all species. In addition to generation of mathematical values for scaling factors, methodological and animal-specific considerations, such as age, sex, and strain differences, have not yet been comprehensively described. Here, we review the current state-of-the-field for microsomal and cytosolic scaling factors, including highlighting areas that may need further description and development, with the intention of drawing attention to key knowledge gaps. The intention is to promote improved accuracy and precision in IVIVE-PBPK, concordance between laboratories, and stimulate work in underserved, but increasingly vital areas.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-24"},"PeriodicalIF":3.4000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Metabolism Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03602532.2025.2462527","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

The use of in-vitro-in-vivo physiologically based pharmacokinetic (IVIVE-PBPK) modeling approaches assists for prediction of first-in animal or human trials. These approaches are underpinned by the scaling factors: microsomal protein per gram (MPPG) and cytosolic protein per gram (CPPG). In addition, IVIVE-PBPK has significant application in the reduction and refinement of live animal models in research. While human scaling factors are well-defined, many preclinical and livestock species remain poorly elucidated or uncharacterized. The MPPG parameter for liver (MPPGL) is the best characterized across all species and is well-defined for mouse, rat, and dog models. The MPPG parameters for Kidney (MPPGK) and intestine (MPPGI), are however; relatively indefinite for most species. Similarly, CPPG scaling factors for liver, kidney, and intestine (CPPGL/CPPGK/CPPGI) are generally sparse in all species. In addition to generation of mathematical values for scaling factors, methodological and animal-specific considerations, such as age, sex, and strain differences, have not yet been comprehensively described. Here, we review the current state-of-the-field for microsomal and cytosolic scaling factors, including highlighting areas that may need further description and development, with the intention of drawing attention to key knowledge gaps. The intention is to promote improved accuracy and precision in IVIVE-PBPK, concordance between laboratories, and stimulate work in underserved, but increasingly vital areas.

求助全文
约1分钟内获得全文 求助全文
来源期刊
Drug Metabolism Reviews
Drug Metabolism Reviews 医学-药学
CiteScore
11.10
自引率
1.70%
发文量
21
审稿时长
1 months
期刊介绍: Drug Metabolism Reviews consistently provides critically needed reviews of an impressive array of drug metabolism research-covering established, new, and potential drugs; environmentally toxic chemicals; absorption; metabolism and excretion; and enzymology of all living species. Additionally, the journal offers new hypotheses of interest to diverse groups of medical professionals including pharmacologists, toxicologists, chemists, microbiologists, pharmacokineticists, immunologists, mass spectroscopists, as well as enzymologists working in xenobiotic biotransformation.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信