Mosekilde Erik, Sosnovtseva Olga V, Holstein-Rathlou Niels-Henrik
Department of Physics, The Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
Basic Clin Pharmacol Toxicol. 2005 Mar;96(3):212-24. doi: 10.1111/j.1742-7843.2005.pto960311.x.
Mechanism-based modeling is an approach in which the physiological, pathological and pharmacological processes of relevance to a given problem are represented as directly as possible. This approach allows us (i) to test whether assumed hypotheses are consistent with observed behaviour, (ii) to examine the sensitivity of a system to parameter variation, (iii) to learn about processes not directly amenable to experimentation, and (iv) to predict system behavior under conditions not previously experienced. The paper illustrates different aspects of the application of mechanism-based modeling through three different examples of relevance to the treatment of diabetes and hypertension: subcutaneous absorption of insulin, pulsatile insulin secretion in normal young persons, and synchronization of the pressure and flow regulation in neighbouring nephrons. The underlying ideas are that each regulatory mechanism represents the target for intervention and that the development of new and more effective drugs must be based on a deeper understanding of the biological processes.
基于机制的建模是一种方法，其中与给定问题相关的生理、病理和药理过程被尽可能直接地表示出来。这种方法使我们能够：（i）测试假设的假说是否与观察到的行为一致；（ii）检查系统对参数变化的敏感性；（iii）了解无法直接进行实验的过程；（iv）预测在以前未经历过的条件下系统的行为。本文通过与糖尿病和高血压治疗相关的三个不同例子，说明了基于机制的建模应用的不同方面：胰岛素的皮下吸收、正常年轻人的脉冲式胰岛素分泌，以及相邻肾单位中压力和流量调节的同步。其基本思想是，每种调节机制都是干预的目标，新的更有效的药物的开发必须基于对生物过程的更深入理解。
