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一种基于生理学的纳米颗粒药物解毒药代动力学模型。

A physiologically-based pharmacokinetic model of drug detoxification by nanoparticles.

作者信息

Fallon Marissa S, Varshney Manoj, Dennis Donn M, Chauhan Anuj

机构信息

Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA.

出版信息

J Pharmacokinet Pharmacodyn. 2004 Oct;31(5):381-400. doi: 10.1007/s10928-004-8322-9.

Abstract

Nanoparticles (NPs) may be capable of reversing the toxic effects of drug overdoses in humans by adsorbing/absorbing drug molecules. This paper develops a model to include the kinetic effects of treating drug overdoses by NPs. Depending on the size and the nature of the NPs, they may either pass through the capillary walls and enter the tissue space or remain only inside the capillaries and other blood vessels: models are developed for each case. Furthermore, the time scale for equilibration between the NP and the blood will vary with the specific type of NP. The NPs may sequester drug from within the capillaries depending on whether this time scale is larger or smaller than the residence time of blood within the capillary. Models are developed for each scenario. The results suggest that NPs are more effective at detoxification if they are confined to the blood vessels and do not enter the tissues. The results also show that the detoxification process is faster if drug uptake occurs within the capillaries. The trends shown by the model predictions can serve as useful guides in the design of the optimal NP for detoxification.

摘要

纳米颗粒(NPs)或许能够通过吸附/吸收药物分子来逆转药物过量对人体产生的毒性作用。本文建立了一个模型,用于纳入纳米颗粒治疗药物过量的动力学效应。根据纳米颗粒的大小和性质,它们可能穿过毛细血管壁进入组织间隙,或者仅留在毛细血管和其他血管内:针对每种情况都建立了模型。此外,纳米颗粒与血液达到平衡的时间尺度会因纳米颗粒的具体类型而有所不同。根据这个时间尺度是大于还是小于血液在毛细血管内的停留时间,纳米颗粒可能会从毛细血管内螯合药物。针对每种情况都建立了模型。结果表明,如果纳米颗粒局限于血管内而不进入组织,它们在解毒方面会更有效。结果还表明,如果药物在毛细血管内被摄取,解毒过程会更快。模型预测显示的趋势可为设计最佳解毒纳米颗粒提供有用的指导。

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