Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds.
Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds.
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DOI：
10.3389/fphar.2016.00181
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发表时间：
2016
影响因子：
5.6
通讯作者：
Salar-Behzadi S
中科院分区：
文献类型：
--
作者：
Fröhlich E;Mercuri A;Wu S;Salar-Behzadi S
现代药物开发策略在化合物的设计以及药代动力学、药效学和毒性参数的估计中使用电子计算机技术。结果的质量取决于软件算法、数据库和输入数据。与对口服药物化合物的吸收、分布、代谢、排泄和毒性的模拟相比，对吸入性物质的药代动力学和药效学预测的研究相对较少。为了计算吸收部位的药物浓度，必须知道肺上皮细胞、肺表面积和分布体积(肺衬里液体)等生理参数。这些参数只能通过侵入性技术和尸检来确定。文献中报道了非常不同的价值。本文综述了用于模拟口服吸入物质的软件程序的现状，重点讨论了颗粒沉积、肺表面和肺衬里液体的测定中存在的问题。沉积和药物吸收的不同表面积很难直接包括在模拟中。由于药物浓度受多个参数的影响，单一参数在模拟中的作用不容易确定。
Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily.