Cimetidine pharmacokinetics in patients with Zollinger-Ellison syndrome

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 93; no. 1; p. 69
• Main Authors: McArthur, K E, Raufman, J P, Seaman, J J, Ziemniak, J A, Gardner, J D, Jensen, R T
• Format: Journal Article
• Language: English
• Published: United States 01-07-1987
• Subjects: Adult; Aged; Cimetidine - administration & dosage; Cimetidine - metabolism; Drug Resistance; Female; Gastric Acid - metabolism; Half-Life; Humans; Intestinal Absorption; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Zollinger-Ellison Syndrome - drug therapy; Zollinger-Ellison Syndrome - metabolism
• ISSN: 0016-5085
• DOI: 10.1016/0016-5085(87)90316-7

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.