Animal pharmacodynamics of omeprazole. A survey of its pharmacological properties in vivo

Scand J Gastroenterol Suppl. 1985:108:23-35. doi: 10.3109/00365528509095817.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / metabolism
  • Anti-Ulcer Agents / pharmacology*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / metabolism
  • Benzimidazoles / pharmacology*
  • Dogs
  • Dose-Response Relationship, Drug
  • Duodenum
  • Gastric Acid / metabolism*
  • Gastric Mucosa / drug effects
  • Injections
  • Injections, Intravenous
  • Omeprazole
  • Pepsinogens / metabolism
  • Rats
  • Stomach / drug effects

Substances

  • Anti-Ulcer Agents
  • Benzimidazoles
  • Pepsinogens
  • Omeprazole