Larsson H, Mattson H, Sundell G, Carlsson E
Scand J Gastroenterol Suppl. 1985;108:23-35. doi: 10.3109/00365528509095817.
In the present paper, a collection of experimental data is presented describing the pharmacological profile of omeprazole mainly in dogs and rats. Omeprazole potently inhibited gastric acid secretion in different experimental models. In the dog, for instance, omeprazole was 2-7 times more potent than cimetidine, depending on the route of administration, and in the rat the difference was even greater. Omeprazole was equally potent against different types of stimulation, whereas cimetidine was not, indicating differences in their mechanisms of action. In the dog, the duration of the antisecretory effect was long and lasted for 3-4 days after a single maximal dose of omeprazole. The inhibitory effect after repeated, daily administration of submaximal doses therefore gradually increased and attained a steady-state level after five doses. Treatment up to one year with very high oral doses did not affect the duration of effect. During long-term treatment with high doses of omeprazole a 10-fold increase in meal-stimulated plasma gastrin levels was recorded. This was probably due to a nearly complete inhibition of acid secretion over 24 hours during the study. The gastrin values returned to control levels within eight days after the end of the treatment. Omeprazole was rapidly absorbed (peak plasma levels were reached within one hour) and the elimination half-life was approximately one hour. In the dog, the gastric antisecretory effect was related to the total dose and the area under the plasma concentration curve, whereas the peak level or the shape of the curve was of minor importance. Omeprazole, given orally to rats, dose-dependently prevented experimentally induced gastric lesions. Neither inhibition of acid secretion, stimulation of gastric bicarbonate secretion nor interference with the synthesis of endogenous prostaglandins seems to be of any great importance for the gastric protective effect of omeprazole. Omeprazole seems to be very specific in its gastric acid antisecretory and gastric protective actions since, apart from a decrease in the rate of gastric emptying found after very high oral doses in the rat, no other general pharmacological effects of omeprazole have been observed. Thus, omeprazole was devoid of histamine H2-receptor blocking properties, did not affect the intestinal transport rate, pancreatic secretion, autonomic control of the cardiovascular system or kidney excretion of hydrogen ions.
在本论文中，呈现了一组实验数据，描述了奥美拉唑主要在犬和大鼠体内的药理学特性。奥美拉唑在不同实验模型中均能有效抑制胃酸分泌。例如，在犬体内，根据给药途径不同，奥美拉唑的效力比西咪替丁强2至7倍，而在大鼠体内，差异更为显著。奥美拉唑对不同类型的刺激均有同等效力，而西咪替丁则不然，这表明它们的作用机制存在差异。在犬体内，单次给予最大剂量的奥美拉唑后，其抗分泌作用持续时间较长，可达3至4天。因此，每日重复给予次最大剂量后，抑制作用会逐渐增强，在五次给药后达到稳态水平。用非常高的口服剂量治疗长达一年并不影响作用持续时间。在长期用高剂量奥美拉唑治疗期间，记录到餐食刺激后的血浆胃泌素水平增加了10倍。这可能是由于在研究期间24小时内胃酸分泌几乎完全受到抑制。治疗结束后八天内，胃泌素值恢复到对照水平。奥美拉唑吸收迅速（一小时内达到血浆峰值水平），消除半衰期约为一小时。在犬体内，胃抗分泌作用与总剂量及血浆浓度曲线下面积相关，而峰值水平或曲线形状则不太重要。给大鼠口服奥美拉唑后，剂量依赖性地预防了实验性诱导的胃部损伤。奥美拉唑的胃保护作用似乎与抑制胃酸分泌、刺激胃碳酸氢盐分泌或干扰内源性前列腺素的合成均无太大关联。奥美拉唑在胃酸抗分泌和胃保护作用方面似乎非常特异，因为除了在大鼠口服非常高剂量后发现胃排空速率降低外，未观察到奥美拉唑有其他一般药理学作用。因此，奥美拉唑没有组胺H2受体阻断特性，不影响肠道转运速率、胰腺分泌、心血管系统的自主控制或肾脏对氢离子的排泄。
