Abstract：
This study investigates the particle size threshold at which the interdigestive migrating motor complex (IMMC) becomes active in gastric emptying for fasted beagle dogs. Enteric-coated granules containing cetirizine dihydrochloride (CET) were prepared in three particle sizes, 200, 660, and 1,200 µm (D50). To mark IMMC timing and water movement from the stomach, enteric-coated aspirin tablets and acetaminophen solution were used. To six fasted beagle dogs with 50 mL of acetaminophen solution was administered each granule size as a multiple-unit and a single enteric-coated aspirin tablet (3-period crossover study). No significant difference in pharmacokinetic parameters of CET after oral administration of different particle sizes was observed. However, the appearance time of CET in plasma with smaller granules (200 and 660 µm) was significantly faster than that of salicylic acid (a major metabolite of aspirin) in all dogs. In the case of the largest granules (1,200 µm), no significant time difference was observed in the appearance of both compounds in plasma. Furthermore, in two dogs, both compounds appeared at the same time, implying IMMC-regulated gastric emptying for the largest CET granules. These results support a particle size threshold between 660 and 1,200 µm for gastric emptying without IMMC action in fasted beagle dogs.
摘要：
这项研究调查了消化间迁移运动复合物（IMMC）在禁食比格犬的胃排空中变得活跃的粒径阈值。制备了三种粒径的含盐酸西替利嗪（CET）的肠溶颗粒，200、660和1,200µm(D50)。为了标记IMMC的时间和胃中的水运动，使用肠溶阿司匹林片剂和对乙酰氨基酚溶液。向六只禁食的比格犬施用50mL对乙酰氨基酚溶液，每个颗粒大小为多个单位和单个肠溶包衣的阿司匹林片剂（3期交叉研究）。口服不同粒径后，CET的药代动力学参数没有显着差异。然而,在所有犬中,CET在颗粒较小(200和660µm)的血浆中的出现时间明显快于水杨酸(阿司匹林的主要代谢产物).在最大颗粒（1,200µm）的情况下，两种化合物在血浆中的出现均未观察到显着的时间差异。此外，两只狗，两种化合物同时出现,暗示IMMC调节的胃排空是最大的CET颗粒。这些结果支持在禁食的比格犬中没有IMMC作用的胃排空的粒度阈值在660和1,200µm之间。
