Hirasawa T, Muraoka T, Karino A, Hayashi M, Awazu S
J Pharmacobiodyn. 1984 Apr;7(4):246-53. doi: 10.1248/bpb1978.7.246.
The in situ single-pass perfusion method in an individual rat was developed to discuss the solvent drag in drug intestinal absorption without the individual differences. In this method the apparent water influx (influx') was used as a measure of solvent drag in the same manner as the previous paper. Consequently the sieving coefficients of salicylic acid and antipyrine in one rat are not significantly different from one but in the other are significantly smaller than one, resulting in 0.6-0.7 in average. And it was also shown that the reflection from the membrane in the solvent drag can be detected more precisely and efficiently by this method than the recirculating method in the previous paper. The D2O absorption clearance (CLD2O) was equal to net water flux as estimated theoretically when the D2O concentration in lumen was equal to that in plasma, indicating that D2O can be absorbed by water absorption even in the absence of the concentration gradient. Estimating the real water influx from the net water flux obtained under such condition, the minimal contribution ratio of the solvent drag to the total absorption clearance of salicylic acid and antipyrine was calculated to be approximately 12%.
为了在无个体差异的情况下探讨药物肠道吸收中的溶剂拖曳作用,开发了一种针对个体大鼠的原位单程灌注方法。在该方法中,表观水流入量(流入量')与前文相同,被用作溶剂拖曳作用的衡量指标。因此,一只大鼠中水杨酸和安替比林的筛滤系数与1无显著差异,但在另一只大鼠中则显著小于1,平均为0.6 - 0.7。并且还表明,与前文的循环方法相比,该方法能够更精确、高效地检测溶剂拖曳作用中来自膜的反射。当肠腔中D2O浓度与血浆中D2O浓度相等时,D2O吸收清除率(CLD2O)等于理论估算的净水通量,这表明即使在没有浓度梯度的情况下,D2O也可通过水吸收进行吸收。根据在此条件下获得的净水通量估算实际水流入量,计算出溶剂拖曳作用对水杨酸和安替比林总吸收清除率的最小贡献率约为12%。