Multilayered dermal subcompartments for modeling chemical absorption.
Multilayered dermal subcompartments for modeling chemical absorption.
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DOI：
10.1080/10629369608032985
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发表时间：
1996-01-01
影响因子：
3
通讯作者：
McDougal, J N
中科院分区：
文献类型：
--
作者：
Bookout, R L Jr;McDaniel, C R;McDougal, J N
化学物质和药物的皮肤渗透是毒理学家和药理学家关注的问题。环境专家试图用防护服和手套或屏障霜来限制化学品的暴露。药物开发人员试图提高化学物质通过皮肤的渗透性，以达到医疗目的。两者都可以使用基于生物学的预测数学模型来帮助理解所涉及的过程。当这些模型基于可在实验室测量的生理和生化参数时，这些模型特别有用。经过适当验证的基于质量守恒、扩散和化学物质流动输运的模型可以预测人类暴露。在本文中，我们建立了两个新的基于生理的药代动力学（PBPK）皮肤模型来预测皮肤蒸汽暴露后大鼠血液中二溴甲烷的浓度。这些新模型改进了对血液浓度的预测，特别是在接触开始时。敏感性分析表明，渗透率常数对血药浓度预测的影响最大，其次是分配系数。经过适当的验证，新模型可用于改进化学或药物渗透的种类、剂量和持续时间的外推。它们还可用于调查和预测皮肤中药物或化学物质的浓度。
Dermal penetration of chemicals and drugs is of concern to both toxicologists and pharmacologists. Environmental professionals try to limit exposure to chemicals using protective clothing and gloves or barrier creams to trap chemicals. Drug developers try to enhance penetration of chemicals through the skin for medical purposes. Both can use predictive biologically-based mathematical models to assist in understanding the processes involved. These models are especially useful when they are based on physiological and biochemical parameters which can be measured in the laboratory. Appropriately validated models based on conservation of mass, diffusion and chemical transport by flow can be predictive of human exposures. In this paper we develop two new physiologically-based pharmacokinetic (PBPK) skin models to predict blood concentrations of dibromomethane in rats after skin-only vapor exposures. These new models improve the predictions of the blood concentrations especially at the beginning of the exposures. Sensitivity analysis shows that the permeability constants followed by partition coefficients have the most impact on blood concentration predictions. With proper validation the new models could be used to improve species, dose, and duration extrapolations of chemical or drug penetration. They could also be used to investigate and predict concentrations of drugs or chemicals in the skin.