Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution
Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution
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DOI：
10.1016/j.jconrel.2007.06.025
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发表时间：
2007-11-06
影响因子：
10.8
通讯作者：
Edelman, Elazer R.
中科院分区：
文献类型：
--
作者：
Balakrishnan, Brinda;Dooley, John F.;Edelman, Elazer R.
全世界有数百万患者接受了药物洗脱支架，以降低支架内再狭窄的风险。这些局部治疗的疗效和毒性取决于动脉药物沉积、分布和滞留。为了检查给药剂量和药物释放动力学如何控制动脉药物摄取，使用计算流体动力学和瞬时药物扩散-对流的原理创建模型。使用植入支架的猪冠状动脉的经验数据验证了药物洗脱的建模预测。当一团药物在几秒钟内释放并耗尽时，预测动脉药物沉积无效，最小。长达一个月的基于支架的药物释放有效地提供了几乎连续的药物水平，但缓慢的药物呈现速率限制了动脉药物摄取。只有当药物释放和吸收的速率匹配时，摄取才最大化，这发生在长达一小时的药物释放中。在增加支架上药物量的两种可能方法中，药物浓度的调节可能会影响动脉药物沉积的幅度，而涂层药物质量的变化会影响释放持续时间。我们证明了药物释放动力学的重要性和管理动脉药物摄取的药物剂量，并提出新的药物输送策略，用于控制时空动脉药物分布。(C)2007 Elsevier B. V.保留所有权利。
Millions of patients worldwide have received drug-eluting stents to reduce their risk for in-stent restenosis. The efficacy and toxicity of these local therapeutics depend upon arterial drug deposition, distribution, and retention. To examine how administered dose and drug release kinetics control arterial drug uptake, a model was created using principles of computational fluid dynarnics and transient drug diffusion-convection. The modeling predictions for drug elution were validated using empiric data from stented porcine coronary arteries. Inefficient, minimal arterial drug deposition was predicted when a bolus of drug was released and depleted within seconds. Month-long stent-based drug release efficiently delivered nearly continuous drug levels, but the slow rate of drug presentation limited arterial drug uptake. Uptake was only maximized when the rates of drug release and absorption matched, which occurred for hour-long drug release. Of the two possible means for increasing the amount of drug on the stent, modulation of drug concentration potently impacts the magnitude of arterial drug deposition, while changes in coating drug mass affect duration of release. We demonstrate the importance of drug release kinetics and administered drug dose in governing arterial drug uptake and suggest novel drug delivery strategies for controlling spatio-temporal arterial drug distribution. (C) 2007 Elsevier B.V. All rights reserved.