Physiologically relevant one-compartment pharmacokinetic models for skin. 1. Development of models.
Physiologically relevant one-compartment pharmacokinetic models for skin. 1. Development of models.
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生理相关的皮肤一室药代动力学模型。
DOI：
10.1021/js970286e
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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：
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作者：
McCarley,KD;Bunge,AL
□许多研究已经使用皮肤的药代动力学（隔室）模型来预测或分析化学品通过皮肤的吸收。在这些研究中，使用了几种不同的速率常数定义。本研究的目的是开发一个通用程序，将房室模型速率常数与皮肤吸收参数（如渗透性和分配系数）联系起来，并评估速率常数的不同定义是否会产生不同的结果。速率常数表达式的开发需要一个一室模型，以匹配一个膜模型在特定条件下。由于膜模型比隔室模型包含更多的信息，所以隔室模型不能在所有方面与膜模型匹配。因此，许多隔室模型（即，速率常数的不同定义），其匹配不同条件的膜模型。使用该程序，开发了11种不同的隔室模型，并将其与四种不同皮肤吸收情景的膜模型进行了比较。与膜模型最接近的隔室模型取决于具体的接触情景和要预测的内容。一个新的隔室模型同意合理的膜模型，考虑的情况下。
□ Many studies have used pharmacokinetic (compartment) models for skin to predict or analyze absorption of chemicals through skin. In these studies, several different definitions of the rate constants were used. The purpose of this study was to develop a general procedure for relating compartment model rate constants to dermal absorption parameters, such as permeability and partition coefficients, and to assess whether different definitions of the rate constants produce different results. Rate constant expressions were developed by requiring a one-compartment model to match a one-membrane model at specific conditions. Because a membrane model contains more information than a compartment model, a compartment model cannot match the membrane model in all respects. Consequently, many compartment models (i.e., different definitions of the rate constants) can be developed which match the membrane model for different conditions. Using this procedure, 11 different compartment models were developed and compared to the membrane model for four different dermal absorption scenarios. The compartment model that most closely matches the membrane model depends on the specific exposure scenario and what is to be predicted. One of the new compartment models agrees reasonably well with the membrane model, for the cases considered.