Is It Important to Model the Impact of Blood Flow on the Dose of Drugs Delivered Transcutaneously?
Is It Important to Model the Impact of Blood Flow on the Dose of Drugs Delivered Transcutaneously?
复制标题
模拟血流对经皮给药药物剂量的影响重要吗？
作者：
G. Clough;R. Gush
法律规定，给药到皮肤的剂量是受控制的。离子导入使用小电流将带电物质驱动到皮肤中。在离子导入过程中离子的电迁移也被证明可以诱导渗透性水流和中性甚至带电分子的对流运动--这一过程被称为电渗透。一般认为，给药的数量取决于所施加电流的大小和持续时间，达到该剂量所需的驱动力(电压)取决于皮肤及其隔间的结构性质。人的皮肤主要由三层组成--表皮、真皮和皮下组织。虽然表皮的角质层及其结构的亲脂性和亲水性区域构成了药物经皮给药的主要限速层，但真皮及其血管系统作为离子载体药物的全身吸收部位，在模拟经皮离子导入转运时面临着最大的挑战。药物进入真皮和真皮内的运动受到许多变量的影响，包括表皮屏障上的扩散和电斥力、蛋白质/受体结合和药物新陈代谢，这些因素共同调节着皮肤中“周围”离子的存在，这些离子构成了决定药物剂量的电流。长期以来，血管内皮细胞对血管扩张剂刺激的反应性评估一直被认为是评估心血管风险的替代指标。我们对健康和疾病中的内皮细胞表型以及对内皮功能的影响或治疗干预的了解，在很大程度上是基于使用生理和药物刺激测量扰动后血管直径和/或外周血管灌注量的变化。如果这些检测要具有临床价值，它们需要是非侵入性的、可重复性的、可重复性的和实验室间标准化的。它们也不应该自己调节内皮血管功能。在微血管水平上，这些测试通常涉及使用反应性充血、局部升温或引入药物以及随后的血管反应监测来扰乱血管系统[2]。将血管活性物质离子导入皮肤，结合激光多普勒血流仪或灌注成像，在研究和临床环境中已被广泛用于血管内皮功能的评估。这项技术公认的优点是，药物输送是非侵入性的和局部的，从而避免了组织扰动和/或全身药物效应，并且通过控制基于库仑在线发表的离子导入电流的持续时间和大小：2008年11月25日
law, the dose of drug delivered to the skin is controlled. Iontophoresis uses a small electric current to drive charged substances into the skin. Electromigration of ions during iontophoresis has also been shown to induce osmotic water flow and the convective movement of neutral or even charged molecules – a process termed electro-osmosis. It is generally held that the quantity of drug delivered depends on the magnitude and duration of the current applied, the driving force (voltage) required to achieve this dose depending on the nature of the structure of the skin and its compartments. Human skin consists of three main layers – the epidermis, dermis and hypodermis. While the stratum corneum of the epidermis, with its structured lipophilic and hydrophilic domains, constitutes the major rate-limiting layer for transdermal delivery of drugs, the dermis and its vasculature, which act as the systemic absorption site for iontophoresed drugs, present the greatest challenge when modelling transdermal iontophoretic transport. The movement of agents into and within the dermis is subject to many variables, including diffusive and electrorepulsive forces at the epidermal barrier, protein/receptor binding and drug metabolism which together modulate the presence of ‘ambient’ ions in the skin that contribute to the current flow which defines drug dose. The assessment of endothelial responsiveness to vasodilator stimuli has long been considered a surrogate by which to evaluate cardiovascular risk. Our understanding of the endothelial phenotype in health and disease and the impact or therapeutic intervention on endothelial function are largely based on the measurement of changes in vessel diameter and/or perfusion in the peripheral vasculature following perturbation using physiological and pharmacological stimuli. These tests need to be non-invasive, reproducible, repeatable and standardized between laboratories if they are to be of clinical value [1] . They also should not modulate endothelial vascular function by themselves. At the level of the microvasculature, these tests generally involve perturbation of the vasculature using reactive hyperaemia, local warming, or introduction of pharmacological agents and the subsequent monitoring of the vasoresponse [2] . Iontophoretic delivery of vaso-active substances to the skin combined with laser Doppler flowmetry or perfusion imaging has been widely used for the assessment of vascular endothelial function in both research and clinical settings. The recognized advantages of the technique are that drug delivery is non-invasive and local, thus avoiding tissue perturbation and/or systemic drug effects, and that, by controlling the duration and magnitude of the iontophoretic current based on Coulomb’s Published online: November 25, 2008
毛细管流出转运抑制对脑体内微透析过程中探针回收率测定的影响。
DOI：
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发表时间：
2001
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
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作者：
Sun,H;Bungay,PM;Elmquist,WF
通讯作者：
Elmquist,WF