Russell Lisa M, Wiedersberg Sandra, Delgado-Charro M Begoña
Department of Pharmacy & Pharmacology, University of Bath, Bath, UK.
Eur J Pharm Biopharm. 2008 Aug;69(3):861-70. doi: 10.1016/j.ejpb.2008.02.002. Epub 2008 Feb 14.
The individual thickness of the stratum corneum is required to normalise drug permeation profiles in dermato-pharmacokinetic studies. The thickness is often estimated using tape-stripping combined with transepidermal water loss measurements. A linear transformation of Fick's first law is used to relate the progressively thinner barrier with the corresponding increase in transepidermal water loss and to estimate the thickness by linear regression. However, the data from an important subset of subjects are poorly fitted to this linear model. This is typically due to the removal of loose outer layers of stratum corneum, which do not contribute significantly to barrier function. This work proposes two alternative non-linear models. All three models were used to fit data from 31 in vivo tape-stripping experiments and their outcomes and goodness-of-fit compared. The results suggest that the linear model may overestimate the stratum corneum thickness and is open to subjectivity regarding the selection of data points to be fitted. The non-linear models satisfactorily fitted all the data, including all data points. No significant differences were found between the thicknesses derived from the two non-linear models. However, the analysis of the goodness-of-fit of the models to the data suggests a preference for a baseline-corrected approach.
在皮肤药代动力学研究中,需要角质层的个体厚度来规范药物渗透曲线。通常使用胶带剥离结合经表皮水分流失测量来估计该厚度。菲克第一定律的线性变换用于将逐渐变薄的屏障与经表皮水分流失的相应增加联系起来,并通过线性回归估计厚度。然而,来自一个重要受试者子集的数据与该线性模型拟合不佳。这通常是由于去除了对屏障功能贡献不大的角质层松散外层。这项工作提出了两种替代的非线性模型。所有三种模型都用于拟合来自31项体内胶带剥离实验的数据,并比较了它们的结果和拟合优度。结果表明,线性模型可能高估了角质层厚度,并且在选择要拟合的数据点方面存在主观性。非线性模型令人满意地拟合了所有数据,包括所有数据点。两种非线性模型得出的厚度之间没有发现显著差异。然而,对模型与数据拟合优度的分析表明,倾向于采用基线校正方法。