定量系统药理学模型:促进罕见病药物开发的潜在工具。

IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacology & Therapeutics Pub Date : 2024-09-28 DOI:10.1002/cpt.3451
Susana Neves-Zaph, Chanchala Kaddi
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引用次数: 0

摘要

罕见病影响着全球数百万人,给药物开发带来了巨大挑战。这是因为这些疾病的患者群体有限,病理生理学独特,传统的临床试验设计难以实现。定量系统药理学(QSP)模型为加快药物开发,尤其是罕见病的药物开发提供了一种前景广阔的方法。QSP 模型提供了虚拟患者的疾病和药物反应的机理表述,可以补充常规应用的经验建模和模拟方法。QSP 模型可以生成实际患者的数字双胞胎,并从机理上模拟罕见病的疾病进展,同时考虑表型异质性。QSP 模型还可以支持基因治疗等各种药物模式的药物开发。本文介绍了具有影响力的 QSP 模型案例研究,以说明它们在支持罕见适应症药物开发的各个方面所具有的价值。随着这些 QSP 模型应用的不断成熟,它们越来越有可能被更广泛地整合到常规药物开发步骤中。这种整合可以为解决罕见病药物开发中的一些固有挑战提供一个强大的框架。
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Quantitative Systems Pharmacology Models: Potential Tools for Advancing Drug Development for Rare Diseases

Rare diseases, affecting millions globally, present significant drug development challenges. This is due to the limited patient populations and the unique pathophysiology of these diseases, which can make traditional clinical trial designs unfeasible. Quantitative Systems Pharmacology (QSP) models offer a promising approach to expedite drug development, particularly in rare diseases. QSP models provide a mechanistic representation of the disease and drug response in virtual patients that can complement routinely applied empirical modeling and simulation approaches. QSP models can generate digital twins of actual patients and mechanistically simulate the disease progression of rare diseases, accounting for phenotypic heterogeneity. QSP models can also support drug development in various drug modalities, such as gene therapy. Impactful QSP models case studies are presented here to illustrate their value in supporting various aspects of drug development in rare indications. As these QSP model applications continue to mature, there is a growing possibility that they could be more widely integrated into routine drug development steps. This integration could provide a robust framework for addressing some of the inherent challenges in rare disease drug development.

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来源期刊
CiteScore
12.70
自引率
7.50%
发文量
290
审稿时长
2 months
期刊介绍: Clinical Pharmacology & Therapeutics (CPT) is the authoritative cross-disciplinary journal in experimental and clinical medicine devoted to publishing advances in the nature, action, efficacy, and evaluation of therapeutics. CPT welcomes original Articles in the emerging areas of translational, predictive and personalized medicine; new therapeutic modalities including gene and cell therapies; pharmacogenomics, proteomics and metabolomics; bioinformation and applied systems biology complementing areas of pharmacokinetics and pharmacodynamics, human investigation and clinical trials, pharmacovigilence, pharmacoepidemiology, pharmacometrics, and population pharmacology.
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