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Publication Record


Cimetidine-associated patent ductus arteriosus is mediated via a cytochrome P450 mechanism independent of H2 receptor antagonism.
Cotton RB, Shah LP, Poole SD, Ehinger NJ, Brown N, Shelton EL, Slaughter JC, Baldwin HS, Paria BC, Reese J
(2013) J Mol Cell Cardiol 59: 86-94
MeSH Terms: Cimetidine, Cytochrome P-450 Enzyme System, Ductus Arteriosus, Patent, Histamine H2 Antagonists, Humans, Immunohistochemistry, Infant, Newborn, Ketoconazole, Polymerase Chain Reaction, Randomized Controlled Trials as Topic, Ranitidine, Receptors, Histamine, Retrospective Studies
Show Abstract · Added April 9, 2015
Persistent patency of the ductus arteriosus (PDA) is a common problem in preterm infants. The antacid cimetidine is a potent antagonist of the H2 histamine receptor but it also inhibits certain cytochrome P450 enzymes (CYPs), which may affect DA patency. We examined whether cimetidine contributes to PDA and is mediated by CYP inhibition rather than H2 blockade. Analysis of a clinical trial to prevent lung injury in premature infants revealed a significant association between cimetidine treatment and PDA. Cimetidine and ranitidine, both CYP inhibitors as well as H2 blockers, caused relaxation of the term and preterm mouse DA. CYP enzymes that are inhibited by cimetidine were expressed in DA subendothelial smooth muscle. The selective CYP3A inhibitor ketoconazole induced greater DA relaxation than cimetidine, whereas famotidine and other H2 antagonists with less CYP inhibitory effects caused less dilation. Histamine receptors were developmentally regulated and localized in DA smooth muscle. However, cimetidine caused DA relaxation in histamine-deficient mice, consistent with CYP inhibition, not H2 antagonism, as the mechanism for PDA. Oxygen-induced DA constriction was inhibited by both cimetidine and famotidine. These studies show that antacids and other compounds with CYP inhibitory properties pose a significant and previously unrecognized risk for PDA in critically ill newborn infants.
Copyright © 2013 Elsevier Ltd. All rights reserved.
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13 MeSH Terms
Randomized, double-blind comparison of famotidine with ranitidine in treatment of acute, benign gastric ulcer disease. Community-based study coupled with a patient registry.
Brazer SR, Tyor MP, Pancotto FS, Brice RS, Garbutt JT, Wildermann NM, Harrell FE, Pryor DB, Liss CL, Root JK
(1989) Dig Dis Sci 34: 1047-52
MeSH Terms: Clinical Trials as Topic, Double-Blind Method, Famotidine, Female, Histamine H2 Antagonists, Humans, Male, Middle Aged, Random Allocation, Ranitidine, Registries, Stomach Ulcer, Thiazoles
Show Abstract · Added February 28, 2014
A multicenter, double-blind, randomized controlled trial comparing the efficacy and safety of famotidine with ranitidine in the treatment of acute, benign gastric ulcer disease was coupled with a community-based gastric ulcer disease registry. One hundred ninety-five patients with endoscopically documented gastric ulcer disease were enrolled in the trial and randomly allocated to treatment with either famotidine 40 mg at bedtime or ranitidine 150 mg twice a day. Healing rates were similar in both groups: at four weeks 49% vs 48%, at six weeks 71% vs 69%, and at eight weeks 83% vs 81% for famotidine and for ranitidine, respectively. Pain relief, antacid tablet use, and adverse experiences were also similar in the two groups. Only 25% of patients entered in the gastric ulcer registry were enrolled in the trial. Given that patients with more severe or complicated gastric ulcer disease should be excluded from controlled trials of new drugs, the screening criteria used in the present study be excluded from findings being representative of a quarter of the patients seen in these practices. Therefore, coupling a patient registry with a clinical trial helps determine the applicability of its results. Famotidine 40 mg at bedtime is an effective and well-tolerated treatment of acute, benign gastric ulcer disease and is comparable in efficacy and safety to ranitidine 150 mg twice a day.
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13 MeSH Terms