Gastric Acid Antisecretory Effect of Two Different Dosage Forms of Omeprazole during Prolonged Oral Treatment in the Gastric Fistula Dog

Abstract

Two series of experiments have been performed in gastric fistula dogs to test the antisecretory effect of two different oral dosage forms of omeprazole: 2 μmol ± kg⁻¹ ± day⁻¹ as a methylcellulose suspension for 8 weeks and 0.5 μmol ± kg⁻¹ ± day⁻¹ in enteric-coated granules (ECG) for 3 weeks. There was an increasing inhibitory effect during the first days of repeated administration of omeprazole, which is in accordance with its long duration of action. The steady-state inhibitory level was reached after five doses. During the 8-week treatment with the omeprazole suspension (2 μmol ± kg⁻¹) the mean maximal inhibitory level (3 h after dose) was 82%, and the mean minimal inhibitory level (24 h after dose) was 35%. With omeprazole in ECG (0.5 μmol ± kg⁻¹) the steady-state maximal inhibition (4th h) was 60%, whereas 40% inhibition remained after 24 h. Thus, a more even inhibitory level over day and night seems to be obtained with the ECG formulation than with the suspension. Basal and food-stimulated plasma gastrin levels were not significantly affected by the treatment with 0.5 μmol ± kg⁻¹, whereas food-stimulated gastrin levels were slightly increased during treatment with 2 μmol ± kg⁻¹. Control levels of acid secretion were reached within 4 days of stopping treatment. In the present studies, in which the inhibition of acid secretion varied over 24 h between approximately 80% and 35% (maximum and minimum), no rebound effects could be detected as measured up to 1 month after cessation of treatment.

Key Words:

• Dog
• enteric-coated granules
• gastric acid secretion
• long-term treatment
• omeprazole