Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-Machi, Kanazawa, Ishikawa, 920-1192, Japan.
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
Sci Rep. 2023 Oct 14;13(1):17454. doi: 10.1038/s41598-023-44742-y.
The drug absorption profile is dependent on the luminal drug concentration, which in turn is influenced by the gastrointestinal (GI) fluid dynamics. In the present study, therefore, we aimed to examine the luminal fluid dynamics by kinetically analyzing fluid absorption and secretion along the GI tract in rats using the in situ closed-loop technique with non-absorbable fluorescein isothiocyanate-dextran 4000 (FD-4) and tritium water labeling ([H]water) under different osmotic conditions. We found that the luminal fluid volume in the jejunum and ileum, but not the colon, gradually decreased and reached a steady state. In contrast, [H]water almost completely disappeared in all intestinal regions. Kinetic analysis revealed the following rank order for the rate constant of fluid secretion: jejunum > ileum > colon, whereas a negligible regional difference was observed in the rate constant of fluid absorption. Fluid secretion under an isosmotic condition (300 mOsm/kg) was higher than that at 0 mOsm/kg in all intestinal regions, though no significant changes in fluid absorption were observed. Thus, the fluid secretion process appears to be the major determinant of the regional differences in GI fluid dynamics. Our findings indicate that the luminal fluid volume is altered as a result of water ingestion, absorption, and secretion, and finally reaches an apparent steady state, which is regulated mainly by the process of fluid secretion.
药物吸收谱取决于腔室内药物浓度，而腔室内药物浓度又受胃肠（GI）流体动力学的影响。因此，在本研究中，我们旨在通过使用原位闭路技术，使用不可吸收的荧光素异硫氰酸酯-葡聚糖 4000（FD-4）和氚水标记（[H]水），在不同渗透条件下，对大鼠胃肠道内的流体吸收和分泌进行动力学分析，以检查腔室内的流体动力学。我们发现，空肠和回肠的腔室内液体体积逐渐减少并达到稳定状态，但结肠则不然。相比之下，[H]水几乎完全消失在所有肠道区域。动力学分析显示，液体分泌的速率常数为：空肠＞回肠＞结肠，而在液体吸收的速率常数方面，区域差异可以忽略不计。在等渗条件（300 mOsm/kg）下的液体分泌高于 0 mOsm/kg 时在所有肠道区域，尽管观察到液体吸收没有明显变化。因此，液体分泌过程似乎是胃肠道流体动力学区域差异的主要决定因素。我们的研究结果表明，腔室内的液体体积由于水的摄入、吸收和分泌而发生变化，最终达到明显的稳定状态，这主要受液体分泌过程的调节。
