Cimetidine pharmacokinetics in patients with Zollinger-Ellison syndrome.
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.
D000328:Adult; D000368:Aged; D002927:Cimetidine / Q000008:administration & dosage / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015043:Zollinger-Ellison Syndrome / Q000188:drug therapy / Q000378:metabolism*
D002927:Cimetidine