A NEW DIFFUSION CHAMBER SYSTEM FOR THE DETERMINATION OF DRUG PERMEABILITY COEFFICIENTS ACROSS THE HUMAN INTESTINAL EPITHELIUM THAT ARE INDEPENDENT OF THE UNSTIRRED WATER LAYER

被引:53
作者
KARLSSON, J [1 ]
ARTURSSON, P [1 ]
机构
[1] UNIV UPPSALA,CTR BIOMED,DEPT PHARMACEUT,BOX 580,S-75123 UPPSALA,SWEDEN
关键词
DRUG ABSORPTION; PERMEABILITY; INTESTINAL EPITHELIUM; CACO-2; UNSTIRRED WATER LAYER; AQUEOUS BOUNDARY LAYER;
D O I
10.1016/0005-2736(92)90312-A
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A new method for determining permeability coefficients, that are independent of the unstirred water layer (UWL), has been developed. The method was used to determine the cellular permeability coefficient of the rapidly absorbed drug testosterone in monolayers of the human intestinal epithelial cell line, Caco-2. Using a new diffusion cell with an effective stirring system based on a gas lift, the cellular permeability coefficient for testosterone was (1.98 +/- 0.13) . 10(-4) cm/s which is 3.5-times higher than the permeability coefficient obtained in the unstirred system. The thickness of the UWL obtained with the well stirred diffusion cell was 52 +/- 4 mum. This value is much lower than those previously reported in various well stirred in vitro models. The calculated cellular permeability of testosterone was 13-23-times lower than that for an UWL of the same thickness as the epithelial cell (17-30 mum). We conclude that the permeability of the epithelial monolayer must be included in calculations of the thickness of
引用
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页码:204 / 210
页数:7
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