Stavchansky S, Martin A, Loper A
Res Commun Chem Pathol Pharmacol. 1979 Apr;24(1):77-85.
The in situ rat gut technique was used to determine 14-C salicylic acid absorption from aqueous solutions containing 20% glycerol, 20% propylene glycol, 10% ethanol, and 20% polyethylylene glycols (PEG) 4000 and 6000. A phosphate buffer solution of salicylic acid served as a control. Observed rate constants for disappearance of activity from the gut are 0.031 min-1 for glycerol, 0.0327 min-1 for PEG 6000, 0.0395 min-1 for propylene glycol, 0.475 min-1 for polyethylene glycol 4000, 0.0558 min-1 for ethanol, and 0.0752 min-1 for the control. The rate of disappearance from the gut is significantly slower than control for 20% glycerol, PEG 4000 and PEG 6000 solutions (p less than or equal to 0.01). Activity disappears more rapidly from 10% ethanol solutions than from PEG 6000 and glycerol (p = 0.01). Water flux into and out of the intestinal lumen was estimated from tritiated inulin concentrations in the perfusate. A trend for increased loss of activity from ethanol and control solutions associated with net water efflux from the intestine was observed. These results suggest that the composition of drug delivery systems may significantly affect the absorption of drugs from solution.
采用原位大鼠肠道技术，测定水杨酸从含有20%甘油、20%丙二醇、10%乙醇以及20%聚乙二醇（PEG）4000和6000的水溶液中的14-C水杨酸吸收情况。水杨酸磷酸盐缓冲溶液作为对照。观察到的肠道中活性物质消失的速率常数分别为：甘油0.031 min-1、PEG 6000 0.0327 min-1、丙二醇0.0395 min-1、聚乙二醇4000 0.475 min-1、乙醇0.0558 min-1、对照0.0752 min-1。对于20%甘油、PEG 4000和PEG 6000溶液，肠道中活性物质的消失速率显著慢于对照（p≤0.01）。10%乙醇溶液中活性物质的消失速度比PEG 6000和甘油溶液更快（p = 0.01）。通过灌注液中氚标记菊粉的浓度估算进出肠腔的水通量。观察到乙醇溶液和对照溶液中活性物质损失增加的趋势与肠道净水流出有关。这些结果表明，药物递送系统的组成可能会显著影响药物从溶液中的吸收。
