Failure of cimetidine in Zollinger-Ellison syndrome.

Both the pharmacokinetics and the pharmacodynamics of cimetidine were investigated in three patients with Zollinger-Ellison syndrome, who were unresponsive to conventional dosing regimens. Doses employed in these patients ranged from 2400 to 5400 mg daily. The poor response to oral cimetidine, as measured by acid secretion and gastric pH, was associated with subtherapeutic and unreliable cimetidine serum concentrations. The response to intravenous cimetidine was only a transient suppression of gastric secretion. The failure of cimetidine to control gastric hypersecretion in these patients was attributed to both a diminished oral bioavailability and a decreased pharmacologic response to the drug.