Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: A full <i>in vitro</i> analysis

DOI Web Site 被引用文献51件
  • Timothy D. Warner
    The William Harvey Research Institute, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, United Kingdom; and Department of Critical Care Medicine, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom
  • Francesco Giuliano
    The William Harvey Research Institute, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, United Kingdom; and Department of Critical Care Medicine, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom
  • Ivana Vojnovic
    The William Harvey Research Institute, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, United Kingdom; and Department of Critical Care Medicine, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom
  • Antoaneta Bukasa
    The William Harvey Research Institute, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, United Kingdom; and Department of Critical Care Medicine, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom
  • Jane A. Mitchell
    The William Harvey Research Institute, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, United Kingdom; and Department of Critical Care Medicine, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom
  • John R. Vane
    The William Harvey Research Institute, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, United Kingdom; and Department of Critical Care Medicine, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom

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<jats:p> The beneficial actions of nonsteroid anti-inflammatory drugs (NSAID) can be associated with inhibition of cyclo-oxygenase (COX)-2 whereas their harmful side effects are associated with inhibition of COX-1. Here we report data from two related assay systems, the human whole blood assay and a modified human whole blood assay (using human A549 cells as a source of COX-2). This assay we refer to as the William Harvey Modified Assay. Our aim was to make meaningful comparisons of both classical NSAIDs and newer COX-2-selective compounds. These comparisons of the actions of >40 NSAIDs and novel COX-2-selective agents, including celecoxib, rofecoxib and diisopropyl fluorophosphate, demonstrate a distribution of compound selectivities toward COX-1 that aligns with the risk of serious gastrointestinal complications. In conclusion, this full <jats:italic>in vitro</jats:italic> analysis of COX-1/2 selectivities in human tissues clearly supports the theory that inhibition of COX-1 underlies the gastrointestinal toxicity of NSAIDs in man. </jats:p>

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