Karino A, Hayashi M, Awazu S, Hanano M
J Pharmacobiodyn. 1982 Sep;5(9):670-7. doi: 10.1248/bpb1978.5.670.
In order to study the solvent drag effect, it was shown that back flux of absorbed drug from blood to intestinal lumen can be ignored but the back flux of water cannot. Then, apparent water influx was calculated as a new measure of solvent drag based on the model in which the back flux of D2O from blood to lumen was considered during absorption. Consequently, the correlation between drug absorption clearance (CLdrug) and apparent water influx was highly significant for benzoic acid, salicylic acid, p-hydroxybenzoic acid, antipyrine, cephalexin (CEX) and cefroxadine (CXD), resulting the high solvent drag effects were detected. The mean values of the slopes in the regression lines of CLdrug versus apparent water influx, i.e., sieving coefficients, were smaller than one for benzoic acid and salicylic acid, but the values were not significantly different from one. The sieving coefficients of the other drugs were significantly smaller than one. From these results, the molecular size dependence in the reflection from the intestinal membrane during absorption was clearly shown. And the intercepts of the regression lines including diffusive permeabilities were found to be significantly different from zero in CEX and CXD. On the basis of the sieving coefficients and intercept values obtained in such ways, the appropriateness of this model was discussed.
为了研究溶剂拖曳效应，结果表明，吸收的药物从血液到肠腔的反向通量可以忽略不计，但水的反向通量不能忽略。然后，基于吸收过程中考虑重水从血液到肠腔反向通量的模型，计算表观水流入量作为溶剂拖曳的一种新度量。因此，苯甲酸、水杨酸、对羟基苯甲酸、安替比林、头孢氨苄（CEX）和头孢沙定（CXD）的药物吸收清除率（CLdrug）与表观水流入量之间的相关性非常显著，表明检测到了较高的溶剂拖曳效应。CLdrug与表观水流入量回归直线的斜率平均值，即筛分系数，对于苯甲酸和水杨酸小于1，但这些值与1没有显著差异。其他药物的筛分系数明显小于1。从这些结果可以清楚地看出吸收过程中肠膜反射的分子大小依赖性。并且发现包括扩散渗透率的回归直线的截距在CEX和CXD中显著不同于零。基于以这种方式获得的筛分系数和截距值，讨论了该模型的适用性。
