Effect of 7 Years’ Daily Oral Administration of Omeprazole to Beagle Dogs

Abstract

Ten beagle dogs were given omeprazole orally at a dose of 0.17 mg/kg (0.5 μmol/kg) daily for 7 years. Six dogs served as controls. Regularly evaluated criteria were clinical signs, body weight, food consumption, rectal temperature, electrocardiography, hematology, blood chemistry, urinalysis, ophthalmoscopy, gastroscopic examination including gastric mucosal biopsy sampling for histological evaluation, pharmacokinetics of omeprazole, and plasma gastrin levels. After approximately 5 years, a quantitative gastric acid secretion test was performed. No treatment-related adverse clinical signs or effects were observed in the dogs, and all animals survived to term. The annual gastroscopy with histological examinations of gastric mucosa did not show any treatment-related changes. At all investigations and in all dogs, the parietal cells were morphologically normal, and there were no changes of pattern or any increase in the number of argyrophil enterochromaffin-like cells compared to the control animals. In the plasma samples collected 24 h after dosing, there were no significant differences in either basal or meal-stimulated gastrin levels between the controls and the omeprazole-treated animals. Peak plasma concentration of omeprazole occurred within 2 h of dosing. The area under the concentration curve (AUC) was not affected by dosing over 7 years and was in good agreement with the AUC in humans given a dose of 20 mg omeprazole daily. Acid secretion tests after 5 years of treatment showed that the mean inhibition of acid secretion by omeprazole 4-7 h after dosing was as expected – about 50%. It is concluded that 7 years’ treatment with omeprazole in dogs, in a dose resulting in clinically relevant plasma concentrations, did not cause any adverse effects in any of the animals. Furthermore, the degree of acid inhibition of a submaximal dose of omeprazole is maintained during long-term treatment without any signs of tachyphylaxis.

The effect of omeprazole on oesophageal pH in dogs during anaesthesia

“…No complications or side effects related with the administration of omeprazole were noticed. This is consistent with the long‐term observation in dogs administered 0.17 mg/kg oral omeprazole which showed no adverse clinical effects even after 7 years of treatment (Safholm and others 1994).…”

“…In human beings, omeprazole should ideally be administered twice before anaesthesia to reach effective plasma concentrations (Escolano and others 1992). In dog, peak plasma concentration of omeprazole has been found to occur within 2 h of dosing (Safholm and others 1994) and the antisecretory effect to last up to 4 days after a single maximal dose (Larsson and others 1985), without adverse clinical signs (Safholm and others 1994).…”

Proton Pump Inhibitors in Veterinary Medicine

“…Nausea, abdominal pain, constipation, flatulence and diarrhea are common side effects in humans (1.5-3% of patients for omeprazole), but most of these effects are not observed in animals (Kaya, 2007;Papich, 2009;Wallacei and Sharkey, 2011). Säfholm et al (1994) orally administered at a dose of 0.17 mg kg −1 to Beagle dogs and a detailed clinical and gastroscopic examination including gastric mucosal biopsy were regularly performed for 7 years. It was concluded that 7 years' treatment with omeprazole in dogs, in a dose resulting in clinically relevant plasma concentrations, did not cause any adverse effects in any of the animals.…”

Animal Models to Study the Role of Long‐Term Hypergastrinemia in Gastric Carcinogenesis

“…The effects of long-term administration of acid inhibitors has not been studied in the Norwegian Lundehund, but beagle dogs have been given omeprazole daily for 7 years [73]. There were no changes in the gastric mucosa at termination including ECL cell numbers, but the dogs receiving omeprazole had similar fasting and meal-stimulated plasma gastrin levels compared to controls which means the dogs had not received an adequate dose of PPI.…”