Singh P, Roberts M S
Department of Pharmacy, University of Queensland, Australia.
J Pharmacol Exp Ther. 1996 Nov;279(2):908-17.
Topically applied compounds can penetrate directly into deeper underlying tissues. In this report, an attempt has been made to establish structure-deep tissue penetration relationships for a variety of solutes with diverse physicochemical properties. Stepwise multiple linear regression analysis was performed with the concentration in the immediately overlying tissue, the solute molecular size and the octanol/water partition coefficient as independent variables. During the initial period of direct penetration, the concentration of any solute in a given tissue was dependent on the concentration in the preceding tissue. The presence of molecular weight and lipophilicity terms as independent variables improved the regressions for some tissues. The solute concentration in the deeper tissues of sacrificed animals was higher for the smaller solutes. Due to the dominance of solute clearance by blood perfusing the tissues, the dependence of solute concentrations in anesthetized animal tissues on size was less than observed for sacrificed animals. The predictions from these regression analyses yielded predictions similar to those based on a physiological pharmacokinetic model. However, only about 50% of the data was explained by both models. Based on the preliminary qualitative and quantitative analysis, deep tissue penetration of solutes after application, as aqueous solutions, to the epidermis is greater for smaller solutes with adequate lipophilicity.
局部应用的化合物可直接渗透到更深层的底层组织中。在本报告中，已尝试针对具有不同物理化学性质的多种溶质建立结构与深层组织渗透之间的关系。以紧邻上层组织中的浓度、溶质分子大小和正辛醇/水分配系数作为自变量进行逐步多元线性回归分析。在直接渗透的初始阶段，给定组织中任何溶质的浓度取决于前一组织中的浓度。分子量和亲脂性项作为自变量的存在改善了某些组织的回归。对于较小的溶质，处死动物深层组织中的溶质浓度更高。由于灌注组织的血液对溶质清除起主导作用，麻醉动物组织中溶质浓度对大小的依赖性小于处死动物。这些回归分析的预测结果与基于生理药代动力学模型的预测结果相似。然而，两个模型仅解释了约50%的数据。基于初步的定性和定量分析，对于具有足够亲脂性的较小溶质，以水溶液形式应用于表皮后，溶质的深层组织渗透更大。
