Development and Update of Quantitative Pharmacology Concepts and Computational Models for a Better Understanding of Drug Fate and Action

该研究计划基于坚实的理论基础，提供数学方法，有助于更好地了解生物系统的潜在机制，健康和病理条件之间的过渡，以及其对外源性化合物的作用/反应。它解决了高度热门的问题，随着数学在药物研究领域发挥的作用越来越大，这些问题变得非常重要。它侧重于开发先进的定量方法，这些方法是将系统药理学与药物计量学（定量药理学）相结合的综合方法的一部分。事实上，历史上在这一领域占主导地位的经验文化正在逐渐消失，为这些补充甚至替代的数学和计算工具提供更多的基础，目的是合理化和量化药物开发和使用。量化药物、患者生物学及其药物行为之间存在的复杂关系是我们感兴趣的核心。在可能的情况下，开发了由研究部分提供营养的具体计算工具，为公共资金的投资回报带来了附加值。该研究计划完全致力于培养全新一代的定量药理学科学家。它包括三条主线，涉及综合数学模型的发展，最常用的药代动力学指标的更新和合理的药理学策略和微创方法在有限的采样背景下，使用生理和药代动力学建模与数学分析的建议。

This research program bases on solid theoretical foundations to provide mathematical methodologies that help gaining better insights into the underlying mechanisms of the biological system, its transition between healthy and pathological conditions, and its action on/reaction with exogenous compounds. It addresses highly topical issues that became very important with the increasing role that mathematics play in the drug research area. It focuses on the development of advanced quantitative methodologies that are part of an integrative approach combining systems pharmacology with pharmacometrics (quantitative pharmacology). In fact, empirical culture, which historically prevailed in this field, is gradually fading to give more ground to these complementary or even alternative mathematical and computational tools, with the aim to rationalize and quantify drug development and use. Quantification of the complex relationship that exists between the drug, the patient biology and his drug behaviour is at the core of our interest. Whenever possible, concrete computational tools, nourished by the research components, are developed and bring an added value for the return on investment of public funds. This research program is fully dedicated to train a whole new generation of quantitative pharmacological scientists. It consists in three main lines, concerned with the development of integrative mathematical models, update of the most used pharmacokinetic metrics and the proposition of rational pharmacological strategies and minimally invasive approaches in a context of limited sampling, using physiological and pharmacokinetic modeling with mathematical analysis.