CALCULATION OF THE AQUEOUS DIFFUSION LAYER RESISTANCE FOR ABSORPTION IN A TUBE - APPLICATION TO INTESTINAL-MEMBRANE PERMEABILITY DETERMINATION
CALCULATION OF THE AQUEOUS DIFFUSION LAYER RESISTANCE FOR ABSORPTION IN A TUBE - APPLICATION TO INTESTINAL-MEMBRANE PERMEABILITY DETERMINATION
复制标题
DOI：
10.1023/a:1015829128646
复制
发表时间：
1991-03-01
影响因子：
3.7
通讯作者：
AMIDON, GL
中科院分区：
文献类型：
--
作者：
KOU, JH;FLEISHER, D;AMIDON, GL
单程肠道灌流技术已被广泛应用于评估大鼠的肠壁通透性。只有在适当考虑水阻的情况下，才能得到无偏膜参数。这一水阻力是根据对流扩散传质模型数值计算的，该模型包括被动传输和载体介导的肠壁传输。水扩散层阻力可用以下形式的函数[图形]最好地描述，其中G(Z)、P(M)*、P(C)*、K(M)和C(O)分别是Graetz数、被动渗透率、载体介导性渗透率、米氏常数和进入管内的药物浓度。星号是通过将渗透常数与R/D相乘而得到的无量纲量，其中R和D分别是半径和药物扩散系数。A、B、C、D和E是通过最小二乘非线性回归方法得到的，在0.001小于或等于G(Z)小于或等于0.50.01小于或等于P(M)*小于或等于10的范围内分别为1.05、1.74、1.27、0.0659和0.377，0.01小于或等于P(C)*小于或等于10，以及0.01小于或等于K(M)/C(O)小于或等于100。在低Graetz范围内，这一水相阻力与由Levich边界层溶液计算出的相一致，这表明理论上的极限是正确的。利用迭代方法，该方程可用于从实验数据中提取膜的本征透过率。
The single-pass intestinal perfusion technique has been used extensively to estimate the wall permeability in rats. The unbiased membrane parameters can be obtained only when the aqueous resistance is properly accounted for. This aqueous resistance was calculated numerically from a convective diffusive mass transfer model, including both passive and carrier-mediated transport at the intestinal wall. The aqueous diffusion layer resistance was shown to be best described by a function of the form,[GRAPHICS]where G(z), P(m)*, P(c)*, K(m), and C(o) are, respectively, Graetz number, passive permeability, carrier-mediated permeability, Michaelis constant, and the drug concentration entering the tube. Asterisked are dimensionless quantities obtained by multiplying the permeability constants with R/D, where R and D being radius and drug diffusivity, respectively. A, B, C, D and E were obtained by a least-squares nonlinear regression method, giving values of 1.05, 1.74, 1.27, 0.0659, and 0.377, respectively, over the range of 0.001 less-than-or-equal-to G(z) less-than-or-equal-to 0.5, 0.01 less-than-or-equal-to P(m)* less-than-or-equal-to 10, 0.01 less-than-or-equal-to P(c)* less-than-or-equal-to 10, and 0.01 less-than-or-equal-to K(m)/C(o) less-than-or-equal-to 100. This aqueous resistance was found to converge to those calculated from Levich's boundary layer solution in low Graetz range, indicating the correct theoretical limit. Using an iteration method, the equation was shown to be useful in extracting the intrinsic membrane permeability from the experimental data.