Computational Biology (Cobi) Tools as a Framework for Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Extrapolation from Rabbit to Human for Ophthalmic Drug Products
计算生物学 (Cobi) 工具作为基于生理学的药代动力学/药效学模型外推从兔到人眼科药品的框架
基本信息
- 批准号:10116143
- 负责人:
- 金额:$ 17.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Project Summary/Abstract:
Evaluating bioequivalence of ophthalmic drug products in humans is challenging for ethical and practical
reasons. Often, animal models are used to evaluate ophthalmic bioequivalence. Unfortunately, methods for
translation of animal model results to humans has proven elusive. There is a critical need to develop
computational tools to assist with interspecies translation. Physiologically-based model extrapolation can provide
a means for explaining interspecies differences in pharmacokinetics (PK) and pharmacodynamics (PD). The
objective of the proposed work is to develop a translational tool framework for capturing interspecies differences
in the PK and PD of ophthalmic drug products using physiologically-based model extrapolation methods. To
facilitate framework development, we will collect physiologically-based rabbit and human ophthalmic PK and PD
models from literature. Model components will be integrated with our existing models to create optimized models.
Our team’s experience in multiscale ophthalmic modeling enables the framework to include models of varying
complexity (compartmental, quasi-3D, 2D and novel 2.5D models), which provides are more complete picture of
potential extrapolation solutions versus implementing a single model type. Model details (i.e. modeled tissues,
segment, complexity, physiological phenomena, etc.) will be organized in a spreadsheet which will include model
capabilities and limitations. In parallel, an opensource database comparing rabbit and human anatomical and
physiological parameter values/value ranges will be created. Collected and optimized rabbit PK and PD models
will be extrapolated/scaled up to human models by changing anatomical, physiological and biophysical
parameter values. Common dosing scenarios (topical and intravitreal administration of solutions, solid
suspensions and emulsions) will be simulated using extrapolated, collected and optimized human ophthalmic
PK and PD models for comparison purposes. Comparison of simulation results will enable identification of the
current translational knowledge gaps. The framework will allow evaluation of potential solutions to closing these
knowledge gaps. This project will enhance public health by improving regulatory confidence, speed and
efficiency in the approval process for new and generic ophthalmic drug products and by decreasing costs to the
public.
项目概要/摘要:
评价眼科药物产品在人体中的生物等效性是具有挑战性的伦理和实践
原因通常,动物模型用于评价眼科生物等效性。不幸的是,
将动物模型结果转化为人类已被证明是难以实现的。迫切需要发展
计算工具来协助物种间的翻译。基于生理学的模型外推可以提供
解释药代动力学(PK)和药效学(PD)种间差异的方法。的
拟议工作的目标是开发一个翻译工具框架,用于捕捉种间差异
使用基于生理学的模型外推方法,研究眼用药品的PK和PD。到
为了促进框架开发,我们将收集基于生理学的兔和人眼科PK和PD
从文学的模式。模型组件将与我们现有的模型集成,以创建优化的模型。
我们的团队在多尺度眼科建模方面的经验使该框架能够包括不同的模型。
复杂性(房室,准3D,2D和新型2.5D模型),提供了更完整的图片
潜在的外推解决方案与实现单一模型类型。模型细节(即建模组织,
段、复杂性、生理现象等)将被组织在一个电子表格,其中将包括模型
能力和局限性。与此同时,一个开源数据库比较了兔子和人类的解剖结构,
将创建生理参数值/值范围。收集和优化的兔PK和PD模型
将通过改变解剖学、生理学和生物物理学,
参数值。常见的给药方案(溶液、固体和玻璃体内给药)
悬浮液和乳剂)将使用外推、收集和优化的人眼
PK和PD模型用于比较。模拟结果的比较将能够识别
目前翻译知识的差距。该框架将允许评估关闭这些设施的潜在解决方案。
知识差距。该项目将通过提高监管信心、速度和
提高新的和仿制的眼科药品批准程序的效率,并降低成本,
公众
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Carrie German其他文献
Carrie German的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Carrie German', 18)}}的其他基金
Understanding Mustard Vesicants Distribution and Toxicity in the Eye Using In Vivo and In Silico Models
使用体内和计算机模型了解芥末糜烂剂在眼中的分布和毒性
- 批准号:
10709188 - 财政年份:2023
- 资助金额:
$ 17.99万 - 项目类别:
A synergistic in vitro-in silico model of the placental barrier for predicting fetal exposure and toxicity of xenobiotic compounds
胎盘屏障的协同体外计算机模拟模型,用于预测胎儿的外源化合物暴露和毒性
- 批准号:
10698740 - 财政年份:2023
- 资助金额:
$ 17.99万 - 项目类别:
Real-Time Quantitation of Transport Across Vascular-Tissue Interfaces in Organ-On-Chip Models Using In Situ Mass Spectrometry
使用原位质谱法实时定量器官芯片模型中跨血管组织界面的运输
- 批准号:
10394501 - 财政年份:2022
- 资助金额:
$ 17.99万 - 项目类别:
An in vitro model for screening penetration of ocular drug products
筛选眼科药品渗透的体外模型
- 批准号:
10546892 - 财政年份:2022
- 资助金额:
$ 17.99万 - 项目类别:
Computational Biology (Cobi) Tools as a Framework for Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Extrapolation from Rabbit to Human for Ophthalmic Drug Products
计算生物学 (Cobi) 工具作为基于生理学的药代动力学/药效学模型外推从兔到人眼科药品的框架
- 批准号:
10166845 - 财政年份:2020
- 资助金额:
$ 17.99万 - 项目类别:
Computational Biology (Cobi) Tools as a Framework for Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Extrapolation from Rabbit to Human for Ophthalmic Drug Products
计算生物学 (Cobi) 工具作为基于生理学的药代动力学/药效学模型外推从兔到人眼科药品的框架
- 批准号:
10461730 - 财政年份:2020
- 资助金额:
$ 17.99万 - 项目类别:
相似国自然基金
Journal of Integrative Plant Biology
- 批准号:31024801
- 批准年份:2010
- 资助金额:24.0 万元
- 项目类别:专项基金项目
相似海外基金
CAREER: Hybridization and radiation: Integrating across phylogenomics, ancestral niche evolution, and pollination biology
职业:杂交和辐射:系统基因组学、祖先生态位进化和授粉生物学的整合
- 批准号:
2337784 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Continuing Grant
Postdoctoral Fellowship: STEMEdIPRF: Understanding instructor and student concepts of race to measure the prevalence of race essentialism in biology education
博士后奖学金:STEMEdIPRF:了解教师和学生的种族概念,以衡量生物教育中种族本质主义的流行程度
- 批准号:
2327488 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Standard Grant
Conference: 2024 Mammalian Synthetic Biology Workshop
会议:2024年哺乳动物合成生物学研讨会
- 批准号:
2412586 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Standard Grant
Conference: Travel Grant for the 28th Annual International Conference on Research in Computational Molecular Biology (RECOMB 2024)
会议:第 28 届计算分子生物学研究国际会议 (RECOMB 2024) 旅费补助
- 批准号:
2414575 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Standard Grant
Collaborative Research: REU Site: Summer Undergraduate Research Program in RNA and Genome Biology (REU-RGB)
合作研究:REU 网站:RNA 和基因组生物学暑期本科生研究计划 (REU-RGB)
- 批准号:
2349255 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Continuing Grant
REU Site: Nature's machinery through the prism of Physics, Biology, Chemistry and Engineering
REU 网站:通过物理、生物、化学和工程学的棱镜观察自然的机器
- 批准号:
2349368 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Standard Grant
Biology Meets Engineering: Expanding Transdisciplinary STEM Education
生物学与工程学的结合:扩展跨学科 STEM 教育
- 批准号:
2342578 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Continuing Grant
NSF Postdoctoral Fellowship in Biology: Investigating a Novel Circadian Time-Keeping Mechanism Revealed by Environmental Manipulation
美国国家科学基金会生物学博士后奖学金:研究环境操纵揭示的新型昼夜节律机制
- 批准号:
2305609 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Fellowship Award
NSF Postdoctoral Fellowship in Biology: Chironomid Bioturbation at Future High Temperature Scenarios and its Effect on Nutrient Fluxes and Bacterial Activity
NSF 生物学博士后奖学金:未来高温场景下的摇蚊生物扰动及其对营养通量和细菌活性的影响
- 批准号:
2305738 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Fellowship Award
NSF Postdoctoral Fellowship in Biology: Understanding the role of dietary toxins in shaping microbial community dynamics in the gut
NSF 生物学博士后奖学金:了解膳食毒素在塑造肠道微生物群落动态中的作用
- 批准号:
2305735 - 财政年份:2024
- 资助金额:
$ 17.99万 - 项目类别:
Fellowship Award