Laboratory of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112, Japan.
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
J Pharm Sci. 2020 Jun;109(6):1863-1866. doi: 10.1016/j.xphs.2020.03.005. Epub 2020 Mar 12.
Previously, 1 mL of purified water (hyposmotic) or saline (isosmotic) which dissolved 200 μM of FITC-dextran (FD-4), a nonabsorbable marker, was orally administered to rats, and luminal concentration-time profile of FD-4 was directly measured. In this study, at first, luminal FD-4 concentration was measured after oral administration of 0.5 mL of FD-4 purified water solution (200 μM). Then, kinetic analysis was conducted to calculate the fluid volume that passed through each segment of the gastrointestinal tract (V), based on the luminal FD-4 concentration-time profiles obtained from 3 different administration groups. In the group of 1 mL purified water administration, most of administered water was absorbed quickly from the duodenum and upper jejunum, whereas group of saline administration (1 mL) showed only a little amount of absorbed in the upper small intestine. In 0.5 mL purified water group, V in the stomach was approximately half compared to that in 1 mL purified water group. However, for small intestine, almost the same values of V were obtained regardless of the dose-volume. Our findings are valuable to improve the quality of in vitro predictive dissolution tools or in silico simulation for predicting oral drug absorption.
先前，1 毫升纯化水（低渗）或生理盐水（等渗）溶解 200μM 的 FITC-葡聚糖（FD-4），一种不可吸收的标记物，被口服给予大鼠，并直接测量 FD-4 的腔内腔浓度-时间曲线。在这项研究中，首先，在口服 0.5 毫升 FD-4 纯化水溶液（200μM）后测量腔内腔 FD-4 浓度。然后，根据从 3 个不同给药组获得的腔内腔 FD-4 浓度-时间曲线，进行动力学分析以计算通过胃肠道每个节段的流体体积（V）。在 1 毫升纯化水给药组中，大部分给予的水很快从十二指肠和上部空肠吸收，而 1 毫升生理盐水给药组（1 毫升）在上部小肠中仅吸收了少量。在 0.5 毫升纯化水组中，胃中的 V 约为 1 毫升纯化水组的一半。然而，对于小肠，无论剂量-体积如何，都获得了几乎相同的 V 值。我们的发现对于提高体外预测溶解工具或体内模拟预测口服药物吸收的质量是有价值的。
