Pharmaceutical Research最新文献_第2页

Hispidulin Isolated from the Leaves of Clerodendrum inerme (L.) Gaertn Suppresses Trigeminovascular System Activation in a Rat Model Mimicking Migraine. 从毛竹叶中分离得到的Hispidulin在模拟偏头痛的大鼠模型中，Gaertn抑制三叉神经血管系统的激活。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-09 DOI: 10.1007/s11095-025-03864-w

Pi-Chuan Fan, Ming Tatt Lee, Tzu-Hsuan Lai, Wei-Jan Huang, Lih-Chu Chiou

{"title":"Hispidulin Isolated from the Leaves of Clerodendrum inerme (L.) Gaertn Suppresses Trigeminovascular System Activation in a Rat Model Mimicking Migraine.","authors":"Pi-Chuan Fan, Ming Tatt Lee, Tzu-Hsuan Lai, Wei-Jan Huang, Lih-Chu Chiou","doi":"10.1007/s11095-025-03864-w","DOIUrl":"https://doi.org/10.1007/s11095-025-03864-w","url":null,"abstract":"Background: Hispidulin (6-methoxy-4',5,7-trihydroxyflavone) is a flavonoid commonly found in various plant products, including the leaves of Clerodendrum inerme (L.) Gaertn (CI). While there's an abundance of literature describing the therapeutic effect of hispidulin and CI in oncological, immunological, and dermatological models, their effect on neuropsychiatric disorders is also of research interest.Objective: The previous reports on the neuroprotective and GABAA receptor positive modulatory effect of hispidulin may render it as a possible novel candidate as an antimigraine agent.Methods: In the present study, we employed the intracisternal instillation of capsaicin in anesthetized rats to induce the activation of trigeminovascular system (TGVS), which mimics the histopathological hallmarks of migraine that include increased neuronal activation in the trigeminal cervical complex (TCC), calcitonin gene-related peptide (CGRP) immunoreactivity in the trigeminal ganglia (TG) and CGRP depletion in the dura mater.Results: Administration of hispidulin (4, 10, and 50 mg/kg, i.p.) significantly reduced all three TGVS activation parameters induced by i.c. capsaicin. However, pre-treatment of a selective antagonist for α6 subunit-containing GABAA receptor, furosemide (20 mg/kg, i.p.), did not significantly reverse the antimigraine effect of hispidulin.Conclusion: To the best of our knowledge, this is the first report on hispidulin's suppressive effect on preclinical model of migraine. Further studies are required to explore the mechanism(s) of the antimigraine effect of hispidulin. However, these findings could potentially guide future clinical studies of hispidulin, with the aim of improving human health.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preclinical Toxicity Study and Tissue Distribution of YSCH- 01 Injection via Intratumoral Injection, Intravenous Injection, and Intraperitoneal Injection in Syrian Hamsters. YSCH- 01注射液瘤内、静脉、腹腔注射对叙利亚仓鼠的临床前毒性研究及组织分布。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-08 DOI: 10.1007/s11095-025-03863-x

Ruoyu Chen, Xian-Long Fang, Hafiz Khuram Raza

{"title":"Preclinical Toxicity Study and Tissue Distribution of YSCH- 01 Injection via Intratumoral Injection, Intravenous Injection, and Intraperitoneal Injection in Syrian Hamsters.","authors":"Ruoyu Chen, Xian-Long Fang, Hafiz Khuram Raza","doi":"10.1007/s11095-025-03863-x","DOIUrl":"https://doi.org/10.1007/s11095-025-03863-x","url":null,"abstract":"Background: Recombinant L-IFN Adenovirus (YSCH-01) is a modified oncolytic adenovirus, which showed good curative effects in a variety of solid tumors. The safety of YSCH-01 needs to be evaluated for non-clinical research.Methods: This toxicity and distribution study of YSCH-01 injection via ITU/IV/IP injection in Syrian Hamster was conducted to prepare an investigational new drug (IND) application. The endpoints included mortality/moribundity, clinical observation, body weight, palpable mass examination, food consumption, ophthalmology, and clinical pathology. Toxicokinetics, ADA test, viral shedding, and tissue bio-distribution were analyzed.Results: The severely toxic dose in 10% of animals was 1 × 1011 VP/animal, > 2 × 1011 VP/kg, and 6.7 × 1011 VP/kg for ITU groups, IV groups and IP groups, respectively. The antibody titers of recombinant L-IFN adenovirus were significantly increased following YSCH-01 administration, and slightly lower during recovery period. YSCH-01 gDNA can be shed through the administration site, saliva and feces, and almost no urine. In the ITU, IV, and IP injection groups, YSCH-01 was distributed in the whole blood and all collected organs with Tmax in most whole blood/tissues of 2.00-4.00 days and L-IFN was detected in all tumor and serum samples, with a Tmax of 2.00-4.00 days, full or partial clearance of YSCH-01 and L-IFN was noted in most tissues/organs or tumor and serum on D28.Conclusions: Our study demonstrated the toxicity and potential toxicity of YSCH-01 in Syrian hamsters and evaluated its tissue distribution in hamsters after a single administration. STD10 results in hamsters support the safety of the estimated dosage for future clinical studies.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Leveraging Model Master Files for Long-Acting Injectables. 更正：利用模型主文件进行长效注入。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 DOI: 10.1007/s11095-025-03832-4

Yuqing Gong, Robert Hopefl, Tonglei Li, Andrew C Hooker, Daniela Amaral Silva, Khondoker Alam, Murray Ducharme, Rebecca Moody, Pratik Saha, Andrew Babiskin

引用次数: 0

Industry Perspectives on Implementation of Model Master File (MMF) Framework for Generics and Innovator Drugs: Opportunities, Challenges and Future Outlook. 仿制药和创新药模型主文件（MMF）框架实施的行业展望：机遇、挑战和未来展望。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-03-12 DOI: 10.1007/s11095-025-03844-0

Sivacharan Kollipara, Markus Friden, Tycho Heimbach, Pratik Saha, Jan De Backer, Tausif Ahmed, Timothy Nicholas

{"title":"Industry Perspectives on Implementation of Model Master File (MMF) Framework for Generics and Innovator Drugs: Opportunities, Challenges and Future Outlook.","authors":"Sivacharan Kollipara, Markus Friden, Tycho Heimbach, Pratik Saha, Jan De Backer, Tausif Ahmed, Timothy Nicholas","doi":"10.1007/s11095-025-03844-0","DOIUrl":"10.1007/s11095-025-03844-0","url":null,"abstract":"Modeling and simulation (M&S) based approaches have proven significant utility in both new drug and generic product development. Considering the plethora of applications of such novel approaches, the concept of model master file (MMF) has been introduced recently to streamline the regulatory submission process as well as to facilitate the use of M&S approaches. The MMF has potential to reduce the applicant's efforts in preparing and submitting modeling-based applications and can result in reduced review timelines. Approved MMF's are considered as reusable, sharable, portable and generalizable and thus can be used by the same applicant in multiple submissions or by multiple applicants. To further increase the understanding of the MMF framework and to understand potential applications, and limitations, the USFDA and the Center for Research on Complex Generics (CRCG, https://www.complexgenerics.org ) co-hosted a hybrid public workshop titled \"Considerations and Potential Regulatory Applications for a Model Master File\". This article summarizes the industry perspectives of MMF implementation from both new drug and generic product development perspectives. With the help of diverse case studies, an effort was made in the manuscript to discuss potential challenges, opportunities and benefits. The objective of this article is to portray industry thinking on the MMF concept and the use and implementation of the concept during drug discovery and development. The views presented in this manuscript are of industry participants present at the workshop and not the industry at large.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"785-794"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leveraging Model Master Files from a Technology Company Perspective: Facilitating Quantitative Medicine in Regulatory Frameworks. 从技术公司的角度利用模型主文件：促进监管框架下的定量医学。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-02-26 DOI: 10.1007/s11095-025-03833-3

Jan De Backer, James Clarke, Hosein Sadafi, William Ganley, Jessica Spires

{"title":"Leveraging Model Master Files from a Technology Company Perspective: Facilitating Quantitative Medicine in Regulatory Frameworks.","authors":"Jan De Backer, James Clarke, Hosein Sadafi, William Ganley, Jessica Spires","doi":"10.1007/s11095-025-03833-3","DOIUrl":"10.1007/s11095-025-03833-3","url":null,"abstract":"Model Master Files (MMFs) offer a much needed approach to integrating computational modelling into drug development and regulatory frameworks, supporting the growth of quantitative medicine. By acting as confidential repositories for validated models, MMFs enable streamlined submissions, model reuse, and context-specific reviews while safeguarding intellectual property. For technology companies (such as software providers), MMFs provide a structured pathway to engage with the FDA, align innovations with regulatory standards, and expand the use of models across diverse applications. A challenge with the current framework is the need to provide the same validation and verification information to multiple drug companies each time the submit an application. With an MMF in place, drug companies can refer to this same document which the technology provider can add to over time. However, challenges persist, including limited direct interaction with the FDA outside (A)NDA submissions and the need for consistent model validation and version management. Addressing these issues through enhanced collaboration and clear guidelines will maximize the potential of MMFs, fostering broader adoption of modelling and simulation in drug development and advancing personalized medicine.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"795-803"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Paving the Path for Increased Technological Innovation, Strategic Decision Making and Regulatory Acceptance of Modeling and Simulation Approaches. 为增加技术创新，战略决策和监管接受建模和仿真方法铺平道路。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 DOI: 10.1007/s11095-025-03868-6

Lanyan Fang, Eleftheria Tsakalozou, James E Polli

引用次数: 0

Using Model Master Files to Support Oral Drug Product Development and Regulatory Submissions. 使用模型主文件支持口服药物产品开发和监管提交。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-05-29 DOI: 10.1007/s11095-025-03865-9

Yi-Hsien Cheng, Arindom Pal, Rebecca Moody, Tycho Heimbach, Viera Lukacova, Nikunjkumar Patel, Gregory Rullo, Yunming Xu, Tausif Ahmed, Essam Kerwash, Lanyan Fang, Fang Wu

{"title":"Using Model Master Files to Support Oral Drug Product Development and Regulatory Submissions.","authors":"Yi-Hsien Cheng, Arindom Pal, Rebecca Moody, Tycho Heimbach, Viera Lukacova, Nikunjkumar Patel, Gregory Rullo, Yunming Xu, Tausif Ahmed, Essam Kerwash, Lanyan Fang, Fang Wu","doi":"10.1007/s11095-025-03865-9","DOIUrl":"10.1007/s11095-025-03865-9","url":null,"abstract":"This report summarizes the proceedings of Session 2 of the two-day public workshop titled \"Considerations and Potential Regulatory Applications for a Model Master File\" hosted by the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) on May 2-3, 2024. The workshop aimed to discuss the frameworks and practical considerations for developing a model master file (MMF) and its applications to support drug product development and streamline regulatory review processes. This report provides a comprehensive and insightful overview of the second session of the workshop titled \"MMF Applications for Oral Dosage Forms\". The presentations, which included several case studies, covered potential frameworks and context of use (COU) of MMFs for oral drug products, practical considerations during model development, validation, and regulatory submission processes, as well as scientific justification for modification on approved MMFs. Additionally, the discussion highlighted the crucial role of global harmonization of MMFs, which can benefit both industry and regulatory authorities by making modeling more resource- and time-efficient while meeting high regulatory standards, ultimately reducing delays in drug development and accelerating the availability of new medicines. MMFs for oral dosage forms are especially advantageous due to the wealth of global resources from various organizations and the opportunity to extend these capabilities to complex generics. Lastly, the session also discussed the potential for using technology to track the lifecycle of accepted MMFs, enabling adaptations and ensuring transparency in their downstream reuse.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"753-763"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Considerations for Regulatory Reusability of Dynamic Tools in the New Drug Development. 新药开发中动态工具监管可重用性的考虑。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-03-04 DOI: 10.1007/s11095-025-03831-5

Jiang Liu, Yuching Yang, Joga Gobburu, Cynthia J Musante, Martin Klein, Liang Zhao, Rajanikanth Madabushi, Hao Zhu

{"title":"Considerations for Regulatory Reusability of Dynamic Tools in the New Drug Development.","authors":"Jiang Liu, Yuching Yang, Joga Gobburu, Cynthia J Musante, Martin Klein, Liang Zhao, Rajanikanth Madabushi, Hao Zhu","doi":"10.1007/s11095-025-03831-5","DOIUrl":"10.1007/s11095-025-03831-5","url":null,"abstract":"Model-informed drug development (MIDD) approaches have become indispensable for new drug development and to address regulatory challenges. Dynamic tools, such as population pharmacokinetics (popPK), physiologically-based pharmacokinetics (PBPK), and quantitative systems pharmacology (QSP) models, are routinely employed to enhance the efficiency of drug development. Recently, the Fit-for-Purpose (FFP) initiative and the Model Master File (MMF) framework have emerged to support model reusability and sharing in regulatory settings. In this manuscript we share key insights from the Session \"Pathways for Regulatory Acceptance of Dynamic Tools in the New Drug Space\" of Workshop \"Considerations and Potential Regulatory Applications for a Model Master File\", hosted by the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) and discuss the considerations for regulatory acceptance of dynamic modeling tools. Presentations at the workshop explored current practices in PBPK model evaluation, the potential for popPK models in bioequivalence (BE) assessments, and the implications of reusing models. Challenges such as context-specific validation, version control, and the impact of scientific and technological advancements on model reuse were emphasized. The workshop underscored the importance of clear regulatory pathways and structured frameworks for the consistent application of reusable models. The MMF's potential to streamline reviews and reduce redundancies was noted, although operational details require further elaboration. Continued collaboration among stakeholders is essential to refine model-sharing practices, enhance model validation processes, and promote transparency, ensuring that MIDD approaches remain robust and adaptable to evolving regulatory needs.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"765-771"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PBPK Modeling to Support Bioavailability and Bioequivalence Assessment in Pediatric Populations. PBPK模型支持儿科人群的生物利用度和生物等效性评估。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1007/s11095-025-03846-y

Fang Wu, Eleftheria Tsakalozou, Gilbert J Burckart, Rebeka Žakelj, Lu Gaohua, Kazuko Sagawa, Viera Lukacova, Siva Vaithiyalingam, Jianghong Fan, Nikoletta Fotaki, Nikunjkumar Patel, Lanyan Fang

{"title":"PBPK Modeling to Support Bioavailability and Bioequivalence Assessment in Pediatric Populations.","authors":"Fang Wu, Eleftheria Tsakalozou, Gilbert J Burckart, Rebeka Žakelj, Lu Gaohua, Kazuko Sagawa, Viera Lukacova, Siva Vaithiyalingam, Jianghong Fan, Nikoletta Fotaki, Nikunjkumar Patel, Lanyan Fang","doi":"10.1007/s11095-025-03846-y","DOIUrl":"10.1007/s11095-025-03846-y","url":null,"abstract":"This report summarizes the proceedings for Session 3 of the one-day public workshop entitled \"Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development\" a jointly sponsored workshop by U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) on October 12, 2023. The theme of this session was the application and relevant considerations for PBPK modeling in supporting bioavailability (BA) and BE assessment in pediatric populations. The takeaway message from this session was that PBPK modeling can support relative BA and BE assessment in pediatrics since such studies are generally performed in adults or healthy subjects. PBPK absorption modeling can incorporate characteristics of the drug substance and formulation as well as pediatric physiology to assess the potential differences in absorption of different formulations in pediatrics for new and generic drugs. It is necessary to consider the totality of data and use all available evidence integrated into a mechanistic PBPK model to support decision-making. Global research efforts are needed to bridge critical data gaps.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"847-855"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Considering Opportunities and Challenges When Implementing the Model Master File Framework - a Meeting Report. 实施模型主文件框架时的机遇与挑战——会议报告。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-03-07 DOI: 10.1007/s11095-025-03839-x

Eleftheria Tsakalozou, Lanyan Fang, Erin Skoda, Timothy Nicholas, Sivacharan Kollipara, Ke Ren, Stella Grosser, Bhagwant Rege, Partha Roy, Hao Zhu, Liang Zhao

引用次数: 0