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Clinical Pharmacokinetics

, Volume 39, Issue 4, pp 295–309 | Cite as

Selection of Drugs to Treat Gastro-Oesophageal Reflux Disease

The Role of Drug Interactions
  • David A. FlockhartEmail author
  • Zeruesenay Desta
  • Subena K. Mahal
Review Articles Drug Interactions

Abstract

Gastro-oesophageal reflux disease is probably the most common acid-peptic disease in Western countries, and the successful treatment of mild to moderate disease with pharmacotherapy has become commonplace. A large number of effective drugs are now available, and so the decision-making process for physicians increasingly relies on considerations other than pure efficacy. Cost, adverse effects and drug interactions have therefore become important, particularly in the most vulnerable patients — children, the elderly and patients who are ill and are taking medications that may influence the efficacy of antireflux therapy.

Important drug interactions with antacids include the prevention of the absorption of antibacterials such as tetracycline, azithromycin and quinolones. H2 antagonists, proton pump inhibitors and prokinetic agents undergo metabolism by the cytochrome P450 (CYP) system present in the liver and gastrointestinal tract. Cimetidine is an inhibitor of CYP3A and it may cause significant interactions with drugs of narrow therapeutic range and low bioavailability that are metabolised by these enzymes. The gastroparietal proton pump inhibitors lansoprazole, omeprazole and pantoprazole are all primarily metabolised by a genetically polymorphic enzyme, CYP2C19, that is absent from approximately 3% of Caucasians and 20% of Asians. These drugs may also interact with CYP3A, but to a lesser extent.

Interactions with prokinetic agents carry the greatest potential for harm. Metoclopramide is a dopamine antagonist that may cause extrapyramidal effects when administered alone at high concentrations, or when coadministered with antipsychotic agents such as haloperidol or phenothiazines. Cisapride is clearly able to prolong the electrocardiographic QT interval and cause lethal ventricular arrhythmias when its metabolism is slowed by interaction with inhibitors of CYP3A, such as erythromycin, ketoconazole or itraconazole.

Keywords

Theophylline Cimetidine Omeprazole Proton Pump Inhibitor Ranitidine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was funded in part by grants R01-GM56898-01 and T32-9M08386 from the National Institute of General Medical Sciences, Bethesda, MD and by a Center for Education and Research in Therapeutics grant from the Agency for Healthcare Policy and Research, Washington, DC, USA.

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© Adis International Limited 2000

Authors and Affiliations

  • David A. Flockhart
    • 1
    Email author
  • Zeruesenay Desta
    • 1
  • Subena K. Mahal
    • 1
  1. 1.Division of Clinical Pharmacology, Departments of Medicine and PharmacologyGeorgetown University Medical CenterUSA

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