Defining the COX inhibitor selectivity of NSAIDS: implications for understanding toxicity

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    93 Citations (Scopus)


    The hypothesis that the anti-inflammatory activity of NSAIDs derives from COX inhibition is well established. It also underpins the accepted mechanism of the gastrointestinal and renal toxicity of NSAIDs. However, in terms of NSAID-induced cardiovascular toxicity, is COX inhibition then guilty by association? Multiple experimental models of COX-1/COX-2 inhibition have enabled ranking of the relative inhibitory activity of NSAIDs. Inhibition is expressed as an IC50 value and the index of COX selectivity as the ratio of the IC50 value for COX-2 and COX-1. These data informed the 'imbalance hypothesis that the cardiovascular risk of NSAIDs results from an imbalance in the detrimental actions of COX-1-derived thromboxane A2 and the beneficial actions of COX-2-derived prostacyclin (PGI2). Data derived from in vitro models used to generate NSAID IC50 values are discussed in the context of the difficulties in defining COX selectivity and hence understanding the toxicity of NSAIDs in current clinical use.

    Original languageEnglish
    Pages (from-to)769-776
    Number of pages8
    JournalExpert Review of Clinical Pharmacology
    Issue number6
    Publication statusPublished - Nov 2010


    • COX selectivity
    • COX-1
    • COX-2
    • human whole blood assay
    • IC values
    • in vitro models
    • NSAIDs
    • time-dependent inhibition


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