Transdermal reverse iontophoresis of valproate: A noninvasive method for therapeutic drug monitoring
Transdermal reverse iontophoresis of valproate: A noninvasive method for therapeutic drug monitoring
复制标题
DOI：
10.1023/a:1025730815971
复制
发表时间：
2003-09-01
影响因子：
3.7
通讯作者：
Guy, RH
中科院分区：
文献类型：
--
作者：
Delgado-Charro, MB;Guy, RH
目的.这项工作的目的是（a）探讨潜在的经皮反向离子电渗治疗药物监测和（B）开发一个“内标”校准程序，使技术完全非侵入性。进行了一系列体外离子电渗实验，其中丙戊酸钠的皮下浓度从21 μ M变化到1 mM。还将谷氨酸以固定浓度引入皮下供体中，作为校准方法的“内标”。正如预期，在阳极受体室中回收了丙戊酸盐和谷氨酸盐阴离子。丙戊酸盐的离子电渗提取通量与皮下浓度呈线性相关。谷氨酸通量是恒定的。因此，提取通量（丙戊酸盐/谷氨酸盐）的比例直接取决于（a）丙戊酸盐皮下浓度和（B）丙戊酸盐皮下浓度比（丙戊酸盐/谷氨酸盐），从而提供了一种完全无创的方法。这项工作证明了反向离子导入法用于非侵入性治疗监测的潜力。感兴趣的分析物和“内标物”的同时定量使得不需要抽取血液样品。
Purpose. The objectives of this work were (a) to explore the potential of transdermal reverse iontophoresis for therapeutic drug monitoring and (b) to develop an "internal standard" calibration procedure so as to render the technique completely noninvasive.Methods. A series of in vitro iontophoresis experiments was performed in which the subdermal concentration of sodium valproate was varied from 21 muM to 1 mM. Glutamic acid was also introduced into the subdermal donor at a fixed concentration to act as an "internal standard" for the calibration method.Results. Both valproate and glutamate anions were recovered, as expected, at the anodal receptor chamber. The iontophoretic extraction flux of valproate was linearly correlated with the subdermal concentration. Glutamate flux was constant. It follows that the ratio of extracted fluxes (valproate/glutamate) was directly dependent upon (a) the subdermal valproate concentration and (b) the subdermal concentration ratio (valproate/glutamate), offering a means, thereby, to a completely noninvasive methodology.Conclusions. This work demonstrates the potential of reverse iontophoresis for noninvasive therapeutic monitoring. The simultaneous quantification of the analyte of interest and of an "internal standard" renders the withdrawal of a blood sample unnecessary.