Larsson H, Carlsson E, Junggren U, Olbe L, Sjöstrand S E, Skånberg I, Sundell G
Gastroenterology. 1983 Oct;85(4):900-7.
The gastric antisecretory properties of omeprazole, a new potent substituted benzimidazole, have been evaluated in dogs and rats. Omeprazole was compared with another benzimidazole, picoprazole (H 149/94), and with the histamine H2-receptor antagonist cimetidine. The intravenous or intraduodenal administration of omeprazole in the gastric fistula dog inhibited histamine- and pentagastrin-stimulated acid secretion. The intravenous and intraduodenal, ED50 values for inhibition of histamine-stimulated secretion were 0.35 and 0.26 mumol/kg, respectively. Omeprazole was found to be approximately 5-10 times more potent than both picoprazole and cimetidine. After oral omeprazole administration in the Heidenhain pouch dog, the ED50 on histamine-stimulated acid secretion was found to be 1.2 mumol/kg, which corresponded to a potency 2 and 3.5 times greater than that of cimetidine and picoprazole, respectively. Measurement of the plasma concentration of unchanged omeprazole revealed an intraduodenal bioavailability of approximately 70% whereas the oral bioavailability was only approximately 15%. This variation is probably a result of partial degradation of omeprazole in the acid gastric juice. Single intraduodenal doses of omeprazole had a long-lasting inhibitory effect on histamine-stimulated acid secretion in the dog. After a dose of omeprazole, which produced total inhibition initially, the antisecretory effect was detectable for 3-4 days. Omeprazole inhibited basal and stimulated acid secretion in the rat. The intravenous ED50 was calculated to be 1.5 mumol/kg, whereas the oral potency was about 10 times lower. The effect in the rat was also of long duration. After a dose giving maximal inhibition, control acid secretion was restored after approximately 13 h.
新型强效取代苯并咪唑类药物奥美拉唑的胃抗分泌特性已在犬和大鼠中进行了评估。将奥美拉唑与另一种苯并咪唑类药物匹考拉唑（H 149/94）以及组胺H2受体拮抗剂西咪替丁进行了比较。在胃瘘犬中静脉内或十二指肠内给予奥美拉唑可抑制组胺和五肽胃泌素刺激的胃酸分泌。静脉内和十二指肠内给予奥美拉唑抑制组胺刺激分泌的ED50值分别为0.35和0.26 μmol/kg。发现奥美拉唑的效力比匹考拉唑和西咪替丁两者约强5至10倍。在海登海因小胃犬口服奥美拉唑后，发现其对组胺刺激胃酸分泌的ED50为1.2 μmol/kg，其效力分别比西咪替丁和匹考拉唑强2倍和3.5倍。对未变化的奥美拉唑血浆浓度的测量显示十二指肠内生物利用度约为70%，而口服生物利用度仅约为15%。这种差异可能是由于奥美拉唑在胃酸中部分降解所致。十二指肠内单次给予奥美拉唑对犬组胺刺激的胃酸分泌具有持久的抑制作用。给予一剂最初产生完全抑制作用的奥美拉唑后，抗分泌作用在3至4天内均可检测到。奥美拉唑抑制大鼠的基础胃酸分泌和刺激胃酸分泌。静脉内ED50计算为1.5 μmol/kg，而口服效力约低10倍。在大鼠中的作用持续时间也很长。给予一剂产生最大抑制作用的药物后，约13小时后恢复对照胃酸分泌。
