Akiyama Y, Nagahara N, Nara E, Kitano M, Iwasa S, Yamamoto I, Azuma J, Ogawa Y
DDS Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries Ltd, Osaka, Japan.
J Pharm Pharmacol. 1998 Feb;50(2):159-66. doi: 10.1111/j.2042-7158.1998.tb06171.x.
When sustained-release adhesive and non-adhesive microspheres which release the same drugs at similar rates are administered orally, drug absorption after administration of adhesive microspheres should, if the gastrointestinal residence of adhesive microspheres is prolonged as a result of mucoadhesion, be higher than that after administration of non-adhesive microspheres. The gastrointestinal transit of oral adhesive microspheres in man has been evaluated pharmacokinetically using furosemide and riboflavin, compounds with limited absorption sites in the upper small intestine. In a preliminary experiment with fasted rats it was confirmed that a higher percentage of the drug remained in the stomach and that plasma drug levels were higher when furosemide was administered in the form of adhesive rather than non-adhesive microspheres. Two kinds of sustained-release microsphere, adhesive and non-adhesive, containing furosemide and riboflavin in hard gelatin capsules were prepared and orally administered to 10 healthy fasted volunteers in a cross-over design. Areas under the plasma concentration-time curves (AUC) were 1.8 times larger for furosemide and urinary recovery was 2.4 times higher for riboflavin when adhesive microspheres rather than when non-adhesive microspheres were used. When adhesive microspheres containing riboflavin were administered to fed volunteers, urinary recovery was 2.1 times higher and mean residence time (MRT) was more prolonged than when the microspheres were administered to fasted volunteers. Adhesive microspheres were found to adhere to the gastric or intestinal mucosa with high affinity in man and rats, resulting in prolonged gastrointestinal residence.
当口服给予以相似速率释放相同药物的缓释黏附性和非黏附性微球时，如果黏附性微球因黏膜黏附作用而使胃肠道滞留时间延长，那么黏附性微球给药后的药物吸收应该高于非黏附性微球给药后的吸收。已利用速尿和核黄素（在小肠上段吸收部位有限的化合物），对人体口服黏附性微球的胃肠道转运进行了药代动力学评估。在一项对禁食大鼠的初步实验中证实，当以黏附性微球而非非黏附性微球的形式给予速尿时，药物在胃内残留的百分比更高，血浆药物水平也更高。制备了两种含速尿和核黄素的硬明胶胶囊缓释微球，即黏附性和非黏附性微球，并采用交叉设计对10名健康禁食志愿者进行口服给药。当使用黏附性微球而非非黏附性微球时，速尿的血浆浓度-时间曲线下面积（AUC）大1.8倍，核黄素的尿回收率高2.4倍。当将含核黄素的黏附性微球给予进食的志愿者时，尿回收率高2.1倍，平均驻留时间（MRT）比给予禁食志愿者时更长。已发现黏附性微球在人和大鼠体内以高亲和力黏附于胃或肠黏膜，从而导致胃肠道滞留时间延长。
