Reverse iontophoresis is a relatively new technique for non-invasive drug monitoring in the body. It involves a small electrical current being passed through the skin to facilitate the movement of small charged ions and polar molecules on the skin's surface where the amount of drug can then be measured and hence an accurate estimate of the blood concentration can be made. In vivo studies for several molecules show that initially large amounts of drug are extracted from the body, which are unrelated to the magnitude of the blood concentration; over time the fluxes of extraction decrease to a level proportional to the steady state blood concentration. This suggests that, at first, the drug is being extracted from some source other than the blood; one such candidate for this source is the dead cells which form the stratum corneum. In this paper, we construct two related mathematical models; the first describes the formation of the drug reservoir in the stratum corneum as a consequence of repeated drug intake and natural death of skin cells in the body. The output from this model provides initial conditions for the model of reverse iontophoresis in which charged ions from both the blood and the stratum corneum reservoir compete for the electric current. Model parameters are estimated from data collected for lithium monitoring. Our models will improve interpretation of reverse iontophoretic data by discriminating the subdermal from the skin contribution to the fluxes of extraction. They also suggest that analysis of the skin reservoir might be a valuable tool to investigate patients' exposure to chemicals including therapeutic drugs.

中文翻译：

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用逆离子电渗疗法对角质层药物储库的形成及其对药物监测的影响进行建模

反向离子电渗疗法是一种用于体内非侵入性药物监测的相对较新的技术。它涉及到流经皮肤的小电流，以促进小电荷离子和极性分子在皮肤表面的运动，然后可以测量药物的量，从而可以准确估计血药浓度。对几种分子的体内研究表明，最初从体内提取了大量药物，这与血药浓度的大小无关。随着时间的流逝，提取流量降低到与稳态血液浓度成比例的水平。这表明，首先，该药物是从血液以外的其他来源提取的；这种来源的一个这样的候选者是形成角质层的死亡细胞。在本文中，我们建立了两个相关的数学模型；第一部分描述了由于反复摄入药物和体内皮肤细胞自然死亡而在角质层中形成药物储库的情况。该模型的输出为反向离子电渗疗法的模型提供了初始条件，在该条件下，来自血液和角质层储层的带电离子争夺电流。模型参数是根据锂监测收集的数据估算的。我们的模型将区分皮下与皮肤对提取通量的贡献，从而改善对反向离子电渗疗法数据的解释。他们还建议，对皮肤贮库的分析可能是调查患者接触包括治疗药物在内的化学物质的宝贵工具。第一部分描述了由于反复摄入药物和体内皮肤细胞自然死亡而在角质层中形成药物储库的情况。该模型的输出为反向离子电渗疗法的模型提供了初始条件，在该条件下，来自血液和角质层储液池的带电离子争夺电流。模型参数是根据锂监测收集的数据估算的。我们的模型将区分皮下与皮肤对提取通量的贡献，从而改善对反向离子电渗疗法数据的解释。他们还建议，对皮肤贮库的分析可能是调查患者接触包括治疗药物在内的化学物质的宝贵工具。第一部分描述了由于反复摄入药物和人体内皮肤细胞自然死亡而在角质层中形成药物储库的情况。该模型的输出为反向离子电渗疗法的模型提供了初始条件，在该条件下，来自血液和角质层储液池的带电离子争夺电流。模型参数是根据锂监测收集的数据估算的。我们的模型将区分皮下与皮肤对提取通量的贡献，从而改善对反向离子电渗疗法数据的解释。他们还建议，对皮肤贮库的分析可能是调查患者接触包括治疗药物在内的化学物质的宝贵工具。