| Abstract: | Although most patients with Zollinger-Ellison syndrome can be effectively treated with histamine H2-receptor antagonists, many patients require large doses of drug to inhibit gastric acid secretion adequately. The purpose of the present study was to compare the pharmacokinetics of a 1200-mg oral dose of cimetidine in 9 patients with Zollinger-Ellison syndrome requiring more than 2.4 g/day of cimetidine with 5 age-matched normal volunteers receiving intravenous pentagastrin infusions. Poor responsiveness to cimetidine in patients with Zollinger-Ellison syndrome has several different causes. The concentration of cimetidine in the blood required to inhibit gastric acid secretion by 50% was markedly increased in 3 of the patients with Zollinger-Ellison syndrome, suggesting parietal cell resistance. One patient showed a substantial decrease in cimetidine absorption and 4 patients had delayed cimetidine absorption. Thus 7 of the 9 patients with Zollinger-Ellison syndrome who required more than 2.4 g/day of cimetidine to inhibit gastric acid secretion had abnormal cimetidine pharmacokinetics. |
