Panunzi Simona, Gaz Claudio, Cibella Fabio, De Gaetano Andrea
Laboratorio di Biomatematica (BioMatLab), Istituto di Analisi dei Sistemi ed Informatica "A. Ruberti", Consiglio Nazionale delle Ricerche, Roma, Italy.
Faculty of Science, Engineering and Computing, Department of Mechanical Engineering, Kingston University, London, United Kingdom.
Front Physiol. 2022 Dec 2;13:1018050. doi: 10.3389/fphys.2022.1018050. eCollection 2022.
PharmacoKinetics (PK) and PharmacoDynamics (PD) mathematical models of inhaled bronchodilators represent useful tools for understanding the mechanisms of drug action and for the individuation of therapy regimens. A PK/PD model for inhaled bronchoactive compounds was previously proposed, incorporating a simplified-geometry approach: the key feature of that model is a mixed compartmental and spatially distributed representation of the kinetics, with the direct computation of representative flow rates from Ohm's law and bronchial diameter profiles. The aim of the present work is the enrichment and validation of this simplified geometry modeling approach against clinical efficacy data. The improved model is used to compute airflow response to treatment for each single virtual patient from a simulated population and it is found to produce very good fits to observed FEV profiles. The model provides a faithful quantitative description of the increasing degree of improvement with respect to basal conditions with continuing administration and with increasing drug dosages, as clinically expected.
吸入性支气管扩张剂的药代动力学（PK）和药效动力学（PD）数学模型是理解药物作用机制和确定治疗方案的有用工具。之前提出了一种用于吸入性支气管活性化合物的PK/PD模型，该模型采用了简化几何方法：该模型的关键特征是动力学的混合房室和空间分布表示，通过欧姆定律和支气管直径剖面直接计算代表性流速。本研究的目的是针对临床疗效数据对这种简化几何建模方法进行完善和验证。改进后的模型用于计算模拟人群中每个虚拟患者对治疗的气流反应，发现该模型与观察到的第一秒用力呼气容积（FEV）曲线拟合得非常好。正如临床预期的那样，该模型提供了关于持续给药和增加药物剂量时相对于基础状况改善程度增加的可靠定量描述。
