Ghelani A, Radziwonik H
Dept. of Pharmacology, Research and Development Laboratories, Loughborough, UK.
Methods Find Exp Clin Pharmacol. 1990 Nov;12(9):613-8.
A novel cannula insert was used to correct erratic emptying in Heidenhain pouch dogs. The insert restored the recovery of histamine or pentagastrin stimulated gastric acid secretion to that obtained from normal emptying pouch dogs, probably by displacing obstructing tissue within the pouch. Use of the insert did not cause any discomfort to the animals, nor did it alter basal secretion. There was no significant difference between the antisecretory activity of single doses of omeprazole in erratic emptying animals fitted with the insert (ED50 = 0.21 mumol/kg) and in dogs with a normal pouch (ED(50) = 0.13 mumol/kg). Use of the insert achieved an earlier steady secretory response which allowed cumulative dosing to be performed in each animal. There was no significant difference between the effect of cumulative (ED50 = 0.24 mumol/kg) and single doses of omeprazole in erratic emptying dogs. Although there was a significant difference between cumulative dosing in erratic emptiers and single dosing in normal animals it should still be possible to use erratic emptiers with the insert for screening purposes.
一种新型套管插入物被用于纠正海登海因袋犬的排空异常。该插入物可能通过移位袋内阻塞组织,使组胺或五肽胃泌素刺激的胃酸分泌恢复到正常排空袋犬的水平。使用该插入物未给动物带来任何不适,也未改变基础分泌。在安装了插入物的排空异常动物(ED50 = 0.21 μmol/kg)和正常袋犬(ED50 = 0.13 μmol/kg)中,单剂量奥美拉唑的抑酸活性无显著差异。使用插入物实现了更早的稳定分泌反应,从而可以在每只动物身上进行累积给药。在排空异常的犬中,累积给药(ED50 = 0.24 μmol/kg)和单剂量奥美拉唑的效果无显著差异。尽管排空异常动物的累积给药与正常动物的单剂量给药之间存在显著差异,但使用带有插入物的排空异常动物进行筛选仍应是可行的。