跨越沟:如何接近菌体剂量的转化药理动力学-药理动力学建模
Gauri G Rao1, Quentin Vallé1, Ramya Mahadevan1
1USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, USA.
Clinical pharmacology and therapeutics
|September 23, 2024
概括
为细菌体 (菌体) 治疗制定最佳剂量策略对于治疗耐药性感染至关重要. 临床前数据的机械建模有助于确定用于有效人体剂量的关键菌体参数.
科学领域:
- 微生物学与传染病的研究
- 药理学和制药科学 药理学和制药科学
- 数学生物学 数学生物学
背景情况:
- 耐多药性细菌感染是一个重大的全球卫生挑战,因为有效的抗菌剂的管道有限.
- 菌体 (菌体) 是一个有前途的治疗替代品,目前正在进行抗生素耐药性感染的临床试验.
- 在人类临床应用中,关于最佳菌体剂量策略的关键知识差距存在.
研究的目的:
- 审查和分析用于理解菌体治疗动态的数学模型.
- 通过基于模型的模拟来确定影响治疗疗效的关键菌体参数.
- 通过告知剂量策略,弥合临床前菌体研究和临床翻译之间的差距.
主要方法:
- 对最近发表的评估菌体治疗的数学模型进行系统审查.
- 在体外和体内临床前数据的分析,为模型开发提供信息,包括细菌/菌体密度和菌体特征 (例如爆裂大小,吸附率).
- 评估包含菌体药理动力学,菌体-抗生素组合和宿主免疫反应 (免疫动力学) 的模型.
主要成果:
- 基于模型的模拟确定了关键的菌体参数,这些参数对于确定有效的剂量方案至关重要.
- 分析显示了研究设计和用于机械模型开发的数据的变化.
- 来自审查模型的见解突显了将药理动力学,药理动力学和免疫动力学数据整合为预测建模的重要性.
结论:
- 机械模型框架对于整合临床前数据来预测菌体治疗结果至关重要.
- 通过建模,识别关键的菌体参数有助于合理设计临床应用的剂量策略.
- 这些建模工作对于将菌体疗法推向成功的临床转化至关重要.
相关概念视频
01:26Pharmacokinetic Models: Comparison and Selection Criterion
49
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
49
01:20Pharmacokinetic Models: Overview
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Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
609
01:06Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
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Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
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01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding
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Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
36
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
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Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
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01:15Model Approaches for Pharmacokinetic Data: Physiological Models
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Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
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