Partitioning, diffusivity and clearance of skin permeants in mammalian dermis
Partitioning, diffusivity and clearance of skin permeants in mammalian dermis
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DOI：
10.1016/j.ijpharm.2007.06.020
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发表时间：
2008-01-04
影响因子：
5.8
通讯作者：
Kasting, Gerald B.
中科院分区：
文献类型：
--
作者：
Kretsos, Kosmas;Miller, Matthew A.;Kasting, Gerald B.
通过分析从文献中获得的体外渗透数据并结合测试渗透剂H-3-睾酮的实验结果，检查了化合物在哺乳动物真皮中的分配系数（K-de）和扩散系数（D-de）。文献数据涉及26个化合物，分子量范围为18 - 476 Da，涉及4个物种：人、豚鼠、大鼠和小鼠。在存在和不存在外部血清白蛋白的情况下，采用离体人真皮通过渗透和解吸测量研究了替吉奥。建立了K-de和D-de的数学模型。K-de模型涉及电离，结合到血管外血清蛋白和分区成一个小的脂质室。D-de模型采用了自由扩散系数与类似液体的大小依赖乘以从K-de导出的结合因子。另一项分析考虑了局部应用渗透剂的体内皮肤浓度曲线。6种渗透物中有5种的文献数据被先前发表的真皮毛细血管清除模型很好地描述，这导致浓度随深度呈指数衰减。计算的衰变长度（Ile值）范围为210 ~ 920 μ m，相应的清除速率常数k（de）范围为0.9 × 10 ~（-4）~ 14 × 10 ~（-4）s ~（-1）（n = 8）。从指数衰减曲线的approachures进行了讨论，在非均匀的毛细管间隙和不完全达到稳态。(C)2007 Elsevier B. V.保留所有权利。
The partition coefficients (K-de) and diffusivities (D-de) of compounds in mammalian dermis were examined through an analysis of in vitro permeation data obtained from the literature combined with experimental results with the test permeant, H-3-testosterone. The literature data involved 26 compounds ranging in molecular weight from 18 to 476 Da and four species-human, guinea pig, rat and mouse. Testosterone was studied by permeation and desorption measurements employing excised human dermis in the presence and absence of external serum albumin. Mathematical models for both K-de and D-de were developed. The K-de model involved ionization, binding to extravascular serum proteins and partitioning into a small lipid compartment. The D-de model employed a free diffusivity with a liquid-like size dependence multiplied by a binding factor derived from K-de,. An additional analysis considered in vivo dermal concentration profiles of topically applied permeants. Literature data for 5 of 6 permeants were shown to be well described by a previously published model for capillary clearance in the dermis, which leads to an exponential decay of concentration with depth. Computed decay lengths (I le values) ranged from 2 10 to 920 mu m, and the corresponding clearance rate constants k(de) ranged from 0.9 x 10(-4) to 14 x 10(-4)s(-1) (n = 8). Departures from the exponential decay profile are discussed in terms of non-uniform capillary clearance and incomplete attainment of a steady-state. (C) 2007 Elsevier B.V. All rights reserved.