Abstract
It has been proposed that two distinct cyclooxygenase (COX) enzymes, COX-1 and COX-2 exist which catalyse the production of physiological and proinflammatory prostaglandins, respectively. This may be significant in the clinical setting, as an NSAID that demonstrates COX-2 selectivity could inhibit the inflammatory response without causing COX-1-mediated gastric or renal complications.
Currently, most NSAIDs inhibit both COX-1 and COX-2 enzymes. However, in isolated enzyme assays using both instantaneous competitive inhibition and the more clinically relevant, time-dependent inhibition methods have demonstrated that etodolac (Lodine) preferentially inhibits COX-2, with an approximate 10-fold selectivity over the COX-1 enzyme. This COX-2 selectivity of etodolac has subsequently been confirmed in cellular assays, human dermal fibroblasts, and human whole blood. Also, the studies showed that certain compounds in development respresenting new classes of NSAIDs (e.g. NS-398 and SC-58125) had COX-2 selectivity.
Of the currently marketed NSAIDs, only etodolac consistently demonstrates COX-2 selectivity, and this may, in part, explain the favourable safety profile of etodolac in animals and man.
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Glaser, K.B. Cyclooxygenase selectivity and NSAIDs: Cyclooxygenase-2 selectivity of etodolac (LODINE). Inflammopharmacology 3, 335–345 (1995). https://doi.org/10.1007/BF02668029
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DOI: https://doi.org/10.1007/BF02668029