将定量和系统药理学应用于药物开发及其他领域:临床药理学家入门

IF 1.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Mathan Kumar Ramasubbu, Bhairav Paleja, Anand Srinivasann, Rituparna Maiti, Rukmini Kumar
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引用次数: 0

摘要

定量与系统药理学(QSP)是一种创新的综合方法,它将生理学与药理学相结合,以加速医学研究。本综述重点介绍 QSP 在药物开发中的关键作用及其更广泛的应用,向临床药理学家/研究人员介绍 QSP 的定量方法及其增强实践和决策的潜力。QSP 的应用历史揭示了它在不同领域的影响,包括葡萄糖调节、肿瘤学、自身免疫疾病和 HIV 治疗。通过同时考虑各种细胞类型的受体-配体相互作用、代谢途径、信号网络和疾病生物标志物,QSP 提供了对人体、疾病和药物之间相互作用的整体理解。跨时间和空间尺度的知识整合增强了通用性,使人们能够深入了解个性化反应和总体趋势。QSP 将大量数据整合到强大的数学模型中,根据临床前数据预测临床试验结果并优化剂量。QSP 在 "学习和确认范式 "下运行,通过整合实验结果来生成可检验的假设,并通过精确的实验设计来完善这些假设。涉及药理学、生物化学、遗传学、数学和医学专业知识的跨学科合作至关重要。QSP 在药物开发、药物反应预测、剂量优化和联合疗法评估等不同阶段的整合应用,证明了 QSP 的实用性。在模型复杂性、交流和同行评审方面存在挑战。标准化的工作流程和评估方法可确保可靠性和透明度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Applying quantitative and systems pharmacology to drug development and beyond: An introduction to clinical pharmacologists

Quantitative and systems pharmacology (QSP) is an innovative and integrative approach combining physiology and pharmacology to accelerate medical research. This review focuses on QSP’s pivotal role in drug development and its broader applications, introducing clinical pharmacologists/researchers to QSP’s quantitative approach and the potential to enhance their practice and decision-making. The history of QSP adoption reveals its impact in diverse areas, including glucose regulation, oncology, autoimmune disease, and HIV treatment. By considering receptor–ligand interactions of various cell types, metabolic pathways, signaling networks, and disease biomarkers simultaneously, QSP provides a holistic understanding of interactions between the human body, diseases, and drugs. Integrating knowledge across multiple time and space scales enhances versatility, enabling insights into personalized responses and general trends. QSP consolidates vast data into robust mathematical models, predicting clinical trial outcomes and optimizing dosing based on preclinical data. QSP operates under a “learn and confirm paradigm,” integrating experimental findings to generate testable hypotheses and refine them through precise experimental designs. An interdisciplinary collaboration involving expertise in pharmacology, biochemistry, genetics, mathematics, and medicine is vital. QSP’s utility in drug development is demonstrated through integration in various stages, predicting drug responses, optimizing dosing, and evaluating combination therapies. Challenges exist in model complexity, communication, and peer review. Standardized workflows and evaluation methods ensure reliability and transparency.

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来源期刊
CiteScore
4.00
自引率
4.20%
发文量
53
审稿时长
4-8 weeks
期刊介绍: Indian Journal of Pharmacology accepts, in English, review articles, articles for educational forum, original research articles (full length and short communications), letter to editor, case reports and interesting fillers. Articles concerning all aspects of pharmacology will be considered. Articles of general interest (e.g. methods, therapeutics, medical education, interesting websites, new drug information and commentary on a recent topic) are also welcome.
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