4.6 Article

Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract

期刊

PARTICLE AND FIBRE TOXICOLOGY
卷 20, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s12989-023-00523-z

关键词

-

向作者/读者索取更多资源

Inhalation is a pathway for aerosol entry into the respiratory tract, where particles accumulate depending on their deposition sites, clearance mechanisms, and solubility. Dissolution of particles is determined by their surface area to volume or mass ratio. Assuming complete dissolution of particles in the alveolar region overestimates the concentration of a compound in blood and underestimates its pulmonary burden. Physiologically based pharmacokinetic modeling can be improved by including estimates of lung burden and particle dissolution over time.
Inhalation is a portal-of-entry for aerosols via the respiratory tract where particulate burden accumulates depending on sites of particle deposition, normal clearance mechanisms, and particle solubility. The time available for dissolution of particles is determined by the balance between the rate of particle clearance from a region and their solubility in respiratory solvents. Dissolution is a function of particle surface area divided by particle volume or mass (i.e., dissolution is inversely proportional to the physical diameter of particles). As a conservative approach, investigators commonly assume the complete and instantaneous dissolution of metals from particles depositing in the alveolar region of the respiratory tract. We derived first-order dissolution rate constants to facilitate biokinetic modeling of particle clearance, dissolution, and absorption into the blood. We then modeled pulmonary burden and total dissolution of particles over time as a function of particle size, density, and solubility. We show that assuming poorly soluble particle forms will enter the blood as quickly as highly soluble forms causes an overestimation of concentrations of the compound of interest in blood and other extrapulmonary tissues while also underestimating its pulmonary burden. We conclude that, in addition to modeling dose rates for particle deposition into the lung, physiologically based pharmacokinetic modeling of pulmonary and extrapulmonary tissues concentrations of moderately and poorly soluble materials can be improved by including estimates of lung burden and particle dissolution over time.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据