Omeprazole. Gastrin and gastric endocrine cell data from clinical studies.
Gastric enterochromaffin-like cell carcinoids have been detected in rats exposed lifelong to omeprazole. By inhibiting acid secretion, omeprazole causes hypergastrinemia which, with prolonged exposure, exerts a trophic effect on enterochromaffin-like cells with eventual enterochromaffin-like cell carcinoid formation in some animals. This mechanism seems to explain the appearance of enterochromaffin-like cell carcinoids in human hypergastrinemic states, whether associated with hyperchlorhydria, eg, Zollinger-Ellison syndrome, or with hypochlorhydria, eg, pernicious anemia (nonantral atrophic gastritis). Omeprazole produces modest serum gastrin elevations in humans when monitored over a 24-hr period. Gastrin levels are markedly lower and less sustained than in the above hypergastrinemic states. Extensive gastric biopsy data from patients enrolled in long-term studies indicate that omeprazole administration is not associated with clinically significant changes in the human oxyntic endocrine cell population. Man and rat differ markedly both in their gastrin response to a given level of acid inhibition and in their response to the trophic influence of gastrin on enterochromaffin-like cells. The rat model is a false indicator of risk in man.
Berlin
R G
RG
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
D002452:Cell Count; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D006801:Humans; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D005755:Gastrins; D009853:Omeprazole