Physiologically relevant one-compartment pharmacokinetic models for skin. 2. Comparison of models when combined with a systemic pharmacokinetic model.
Physiologically relevant one-compartment pharmacokinetic models for skin. 2. Comparison of models when combined with a systemic pharmacokinetic model.
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生理相关的皮肤一室药代动力学模型。
DOI：
10.1021/js9702877
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Bunge,AL
中科院分区：
文献类型：
--
作者：
Reddy,MB;McCarley,KD;Bunge,AL
化学品通过皮肤的运输最好模拟为通过膜的被动扩散，但现实条件下的数学解决方案很麻烦。将皮肤表示为搅拌槽的舒适模型在数学上更简单，但与生理相关性较低。在之前的论文中，假设血液和溶剂浓度恒定，开发了几种不同的房室模型。在此，将五种皮肤模型（四种先前描述的隔室模型和一种膜模型）与一室全身药代动力学（PK）模型组合，以检查改变溶媒和血液浓度的影响，并阐明皮肤模型之间的差异如何影响预测的全身反应。使用相同的输入参数（即，渗透系数、分配系数、皮肤厚度和皮肤血流速率），并对五种不同的暴露情况进行比较。由于这些模型有不同的基本假设，它们确实预测了不同的结果。对于许多暴露情况，隔室模型给出了可接受的结果，在短暴露时间内与膜模型的差异最明显。一般来说，最接近代表膜模型的隔室模型是通过强迫它在类似于给定暴露情景的条件下与膜模型相匹配而开发的。
□ Transport of chemicals through skin is best modeled as passive diffusion through a membrane, but mathematical solutions for realistic conditions are cumbersome. Compartment models, representing skin as a stirred tank, are mathematically simpler but less physiologically relevant. In a previous paper, several different compartment models were developed assuming constant blood and vehicle concentrations. Here, five skin models (four of the previously described compartment models and one membrane model) are combined with a one-compartment systemic pharmacokinetic (PK) model to examine the effects of changing vehicle and blood concentrations and to clarify how differences between skin models affect the predicted systemic response. The skin–PK models were solved with the same input parameters (i.e., permeability coefficients, partition coefficients, skin thickness, and cutaneous blood flow rates) and compared for five different exposure scenarios. Because the models have different underlying assumptions, they do predict different results. For many exposure situations compartment models give acceptable results, with the most pronounced differences from the membrane model during short exposure times. Generally, the compartment model that most closely represents the membrane model was developed by forcing it to match the membrane model for conditions similar to those of the given exposure scenario.