Mahendra Chougule, Sivacharan Kollipara, Smritilekha Mondal, Tausif Ahmed
{"title":"关于为基于生理的药物动力学模型生成和验证虚拟群体的方法的重要综述:方法、案例研究和前进方向。","authors":"Mahendra Chougule, Sivacharan Kollipara, Smritilekha Mondal, Tausif Ahmed","doi":"10.1007/s00228-024-03763-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>In silico modeling and simulation techniques such as physiologically based pharmacokinetic (PBPK) and physiologically based biopharmaceutics modeling (PBBM) have demonstrated various applications in drug discovery and development. Virtual bioequivalence leverages these computation tools to predict bioequivalence between reference and test formulations thereby demonstrating possibilities to reduce human studies. A pre-requisite for virtual bioequivalence is development of validated virtual population that depicts the same variability as that of observed in clinic. This development, validation and optimization of virtual population is a key attribute of virtual bioequivalence based on which conclusion of bioequivalence is made.</p><p><strong>Methods: </strong>Various strategies for optimization of virtual population based on appropriate considerations of physicochemical, physiological and disposition aspects are demonstrated with the help of six diverse case studies of immediate and modified release formulations. Once the virtual population is optimized to match in vivo variability, it can be used for various applications such as biowaivers, dissolution specification justification, f2 mismatch, establishing dissolution safe space, etc. In this review article, we attempted to describe various methodologies and approaches for optimization of virtual population using Gastroplus.</p><p><strong>Results: </strong>Strategies based on optimization of virtual population with emphasis on specific and sensitive parameters were portrayed. We have further elucidated considerations related to study design, in vivo variability, sample size for optimization of virtual population from Gastroplus perspective.</p><p><strong>Conclusion: </strong>We believe that this review article provides a step-by-step process for virtual population optimization for interest of biopharmaceutics modeling scientists in order to ensure reliable and credible physiological models.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1903-1922"},"PeriodicalIF":2.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A critical review on approaches to generate and validate virtual population for physiologically based pharmacokinetic models: Methodologies, case studies and way forward.\",\"authors\":\"Mahendra Chougule, Sivacharan Kollipara, Smritilekha Mondal, Tausif Ahmed\",\"doi\":\"10.1007/s00228-024-03763-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>In silico modeling and simulation techniques such as physiologically based pharmacokinetic (PBPK) and physiologically based biopharmaceutics modeling (PBBM) have demonstrated various applications in drug discovery and development. Virtual bioequivalence leverages these computation tools to predict bioequivalence between reference and test formulations thereby demonstrating possibilities to reduce human studies. A pre-requisite for virtual bioequivalence is development of validated virtual population that depicts the same variability as that of observed in clinic. This development, validation and optimization of virtual population is a key attribute of virtual bioequivalence based on which conclusion of bioequivalence is made.</p><p><strong>Methods: </strong>Various strategies for optimization of virtual population based on appropriate considerations of physicochemical, physiological and disposition aspects are demonstrated with the help of six diverse case studies of immediate and modified release formulations. Once the virtual population is optimized to match in vivo variability, it can be used for various applications such as biowaivers, dissolution specification justification, f2 mismatch, establishing dissolution safe space, etc. In this review article, we attempted to describe various methodologies and approaches for optimization of virtual population using Gastroplus.</p><p><strong>Results: </strong>Strategies based on optimization of virtual population with emphasis on specific and sensitive parameters were portrayed. We have further elucidated considerations related to study design, in vivo variability, sample size for optimization of virtual population from Gastroplus perspective.</p><p><strong>Conclusion: </strong>We believe that this review article provides a step-by-step process for virtual population optimization for interest of biopharmaceutics modeling scientists in order to ensure reliable and credible physiological models.</p>\",\"PeriodicalId\":11857,\"journal\":{\"name\":\"European Journal of Clinical Pharmacology\",\"volume\":\" \",\"pages\":\"1903-1922\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00228-024-03763-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00228-024-03763-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/8 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
A critical review on approaches to generate and validate virtual population for physiologically based pharmacokinetic models: Methodologies, case studies and way forward.
Purpose: In silico modeling and simulation techniques such as physiologically based pharmacokinetic (PBPK) and physiologically based biopharmaceutics modeling (PBBM) have demonstrated various applications in drug discovery and development. Virtual bioequivalence leverages these computation tools to predict bioequivalence between reference and test formulations thereby demonstrating possibilities to reduce human studies. A pre-requisite for virtual bioequivalence is development of validated virtual population that depicts the same variability as that of observed in clinic. This development, validation and optimization of virtual population is a key attribute of virtual bioequivalence based on which conclusion of bioequivalence is made.
Methods: Various strategies for optimization of virtual population based on appropriate considerations of physicochemical, physiological and disposition aspects are demonstrated with the help of six diverse case studies of immediate and modified release formulations. Once the virtual population is optimized to match in vivo variability, it can be used for various applications such as biowaivers, dissolution specification justification, f2 mismatch, establishing dissolution safe space, etc. In this review article, we attempted to describe various methodologies and approaches for optimization of virtual population using Gastroplus.
Results: Strategies based on optimization of virtual population with emphasis on specific and sensitive parameters were portrayed. We have further elucidated considerations related to study design, in vivo variability, sample size for optimization of virtual population from Gastroplus perspective.
Conclusion: We believe that this review article provides a step-by-step process for virtual population optimization for interest of biopharmaceutics modeling scientists in order to ensure reliable and credible physiological models.
期刊介绍:
The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed.
Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor.
Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves
-a compound that is interesting and new in some basic or fundamental way, or
-methods that are original in some basic sense, or
-a highly unexpected outcome, or
-conclusions that are scientifically novel in some basic or fundamental sense.