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Abstract
Omeprazole is a substituted benzimidazole which blocks gastric acid secretion by inhibiting H+K+ATPase. Radioactive omeprazole was given intravenously or orally to mice, and the distribution of the drug was investigated at various intervals by scintillation counting and by autoradiography. The half-life for radioactivity in the stomach was 14 hours versus 30–36 hours in the liver, kidneys and blood. At 16 hours after the drug was given, the radioactivity in the stomach was ten times higher than that in the liver and kidneys, and 100 times that in the blood. Whole-body autoradiography showed sustained high levels of radioactivity only in the gastric mucosa. Light microscopic autoradiographic investigations of the gastric mucosa from mice killed 1 or 16 hours after the drug was given revealed radioactivity in the parietal cells. By electron microscopy of gastric mucosa from the mouse killed 16 hours after omeprazole injection the isotope label was found mainly over the secretory surface and the tubulo-vesicles. At these locations H+K+ATPase has previously been demonstrated, and it is suggested that omeprazole—or its metabolites—binds to this enzyme.