Modeling bioavailability to organs protected by biological barriers.
Modeling bioavailability to organs protected by biological barriers.
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DOI：
10.1186/2193-9616-1-8
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Quignot N
中科院分区：
文献类型：
--
作者：
Quignot N
计算药代动力学（PK）建模可以获得靶器官中的药物浓度与时间曲线，并可以更好地解释治疗或毒性作用的临床观察结果。特别是基于身体解剖学和生理学的机制描述的基于生理学的PK（PBPK）模型也可以帮助将体外或动物数据外推到人类。一旦进入体循环，化学物质就可以进入每个器官或组织的微血管系统。然而，其在脑、视网膜、胸腺、脊髓、睾丸、胎盘中的渗透可能受到动态生理血液组织屏障的限制甚至完全阻止。这些屏障既有物理的（涉及相邻细胞之间的紧密连接），也有生物化学的（涉及代谢酶和转运蛋白）。在这些情况下，分子通过（或不通过）屏障的正确机制表征对于改进PBPK建模和预测至关重要。同时，试图了解和定量表征药物渗透生理屏障的过程，导致了几个体外实验模型的发展。来自此类测定的数据对于校准PBPK模型非常有用。我们在这里回顾那些在体外和计算模型，强调的挑战和前景，在体外和计算模型，以更好地评估药物对靶组织的可用性。
Computational pharmacokinetic (PK) modeling gives access to drug concentration vs. time profiles in target organs and allows better interpretation of clinical observations of therapeutic or toxic effects. Physiologically-based PK (PBPK) models in particular, based on mechanistic descriptions of the body anatomy and physiology, may also help to extrapolate in vitro or animal data to human. Once in the systemic circulation, a chemical has access to the microvasculature of every organ or tissue. However, its penetration in the brain, retina, thymus, spinal cord, testis, placenta,… may be limited or even fully prevented by dynamic physiological blood-tissue barriers. Those barriers are both physical (involving tight junctions between adjacent cells) and biochemical (involving metabolizing enzymes and transporters). On those cases, correct mechanistic characterization of the passage (or not) of molecules through the barrier can be crucial for improved PBPK modeling and prediction. In parallel, attempts to understand and quantitatively characterize the processes involved in drug penetration of physiological barriers have led to the development of several in vitro experimental models. Data from such assays are very useful to calibrate PBPK models. We review here those in vitro and computational models, highlighting the challenges and perspectives for in vitro and computational models to better assess drug availability to target tissues.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
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影响因子：
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DOI：
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4.1
作者：
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