Impact of transport and drug properties on the local pharmacology of drug-eluting stents.
Impact of transport and drug properties on the local pharmacology of drug-eluting stents.
复制标题
运输和药物特性对药物洗脱支架局部药理学的影响。
DOI：
10.1080/14628840304614
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Edelman,ElazerR
中科院分区：
文献类型：
--
作者：
Hwang,Chao-Wei;Wu,David;Edelman,ElazerR
从支架释放的药物由生理运输力驱动，主要是溶剂驱动的流动（对流）和随机分子搅动（扩散）。这两种力的相对强度决定了药物在动脉壁中的渗透和分布。药物的理化因素可以诱导关键的调制的主要分布，无论是在短暂的和稳定的状态。例如，疏水相互作用和非特异性结合都可以导致组织药物浓度比给药浓度高几倍。药物与天然蛋白质的相互作用也可能干扰支架-动脉界面处的药物转移。这些转运力和组织相互作用可以诱导局部药物浓度，即使在稳态下，在几个细胞的跨度上也会发生一个或多个数量级的变化。为了解释基于支架的递送后药物浓度的显著局部变化，血管递送系统的合理设计需要在局部、连续的基础上考虑药物分布和组织相互作用。连续分析通过用浓度、转运和结合的连续局部值补充药物含量的离散全局参数来使传统的药代动力学适应局部环境。这些参数与局部通量条件以及药物和组织性质的相互作用定义了局部药物在空间和时间上的分布。考虑到心血管护理中基于支架的药物治疗的趋势，这种类型的分析可能会变得越来越相关。
Drugs released from stents are driven by physiological transport forces, principally solvent-driven flow (convection) and random molecular agitation (diffusion). The relative strength of these two forces determines drug penetration and distribution in the arterial wall. Drug physicochemical factors can induce critical modulations to the primary distribution, both transiently and at steady state. Hydrophobic interactions and nonspecific binding, for example, can both result in tissue drug concentrations severalfold above administered concentration. Drug interaction with native proteins may also interfere with drug transfer at the stent-artery interface. These transport forces and tissue interactions can induce local drug concentrations even at steady state to vary by one or more orders of magnitude over the span of a few cells. To account for significant local variations in drug concentrations following stent-based delivery, rational design of vascular delivery systems requires consideration of drug distribution and tissue interactions on a local, continuum basis. Continuum analysis adapts traditional pharmacokinetics to the local environment by supplementing discrete global parameters of drug content with continuous local values of concentration, transport and binding. The interplay of these parameters with local flux conditions and drug and tissue properties defines the local drug distribution in space and over time. This type of analysis may well become increasingly relevant given the trend toward stent-based drug therapy in cardiovascular care.