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Analysis, interpretation, and extrapolation of dermal permeation data using diffusion-based mathematical models.

Research paper by Jacob J Krüse, Darach D Golden, Simon S Wilkinson, Faith F Williams, Sanja S Kezic, John J Corish

Indexed on: 03 Nov '06Published on: 03 Nov '06Published in: Journal of Pharmaceutical Sciences



Abstract

New dermal penetration data have been measured in both "infinite" and finite dose experiments on a range of compounds of varying lipophilicities. The data are analyzed, using parameter fitting, to determine the values of parameters governing the overall skin absorption processes. Two one-dimensional diffusion models are used. The first is novel, and well suited to the modeling of dermal uptake in occupational exposure scenarios. The second is an implementation of a model taken from the literature. The models are compared in a variety of exposure scenarios, and exhibit good mutual agreement. Both successfully reproduce expected features of the absorption process. Penetration parameters are determined by analyzing both infinite and finite dose data. Prediction of dermal absorption with finite dose scenarios is carried out and compared with experimental data obtained under these conditions. Parameters determined may also have an important role in improving the reliability of predictive QSARs used to estimate the extent of penetration of untested molecules.