Frum Yakov, Eccleston Gillian M, Meidan Victor M
Division of Pharmaceutical Sciences, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, UK.
J Pharm Pharmacol. 2008 Feb;60(2):145-51. doi: 10.1211/jpp.60.2.0002.
It is already well-established that the general permeability properties of porcine skin are close to those of human skin. However, very little is known with respect to drug absorption into hair follicles and the similarities if any between the two types of tissue. The aim of this study was to use the skin sandwich system to quantify follicular drug absorption into porcine hair follicles. To our knowledge, this is the first time that the skin sandwich has been extended to porcine tissue. For this purpose, seven different drugs -- estradiol, corticosterone, hydrocortisone, aldosterone, cimetidine, deoxyadenosine and adenosine -- exhibiting a wide range of log octanol-water partition coefficients (log K(o/w)), but comparable molecular weights, were chosen as candidate solutes. The results showed a parabolic profile with maximal follicular contribution occurring at intermediate log K(o/w) values. Linear regression analysis indicated that the follicular contributions in porcine skin correlated well with previously published follicular contributions in human skin (r(2) = 0.87). The novelty of this research is that we show that porcine tissue is a good surrogate for modelling human skin permeability within the specific context of quantifying drug absorption into hair follicles.
猪皮肤的一般渗透特性与人类皮肤相近,这一点早已得到充分证实。然而,关于药物进入毛囊的吸收情况以及这两种组织之间(若存在)的相似性,人们却知之甚少。本研究的目的是利用皮肤三明治系统来量化药物向猪毛囊的毛囊吸收情况。据我们所知,这是首次将皮肤三明治系统扩展应用于猪组织。为此,选择了七种不同的药物——雌二醇、皮质酮、氢化可的松、醛固酮、西咪替丁、脱氧腺苷和腺苷——这些药物具有广泛的正辛醇 - 水分配系数(log K(o/w)),但分子量相当,作为候选溶质。结果显示出一种抛物线型分布,在中等log K(o/w)值时毛囊贡献最大。线性回归分析表明,猪皮肤中的毛囊贡献与先前发表的人类皮肤中的毛囊贡献具有良好的相关性(r(2) = 0.87)。本研究的新颖之处在于,我们表明在量化药物向毛囊的吸收这一特定背景下,猪组织是模拟人类皮肤渗透性的良好替代物。