Abstract
Tolfenamic acid and tenidap have been reported to be dual inhibitors of cyclo-oxygenase and 5-lipoxygenase. In this study inhibition of 5-lipoxygenase by tenidap and tolfenamic acid in plasma-free leukocyte suspensions (IC50 values = 10 microM) required concentrations more than 100 fold higher than those which inhibited cyclo-oxygenase (IC50 values = 0.05 and 0.02 microM respectively). The potencies of tolfenamic acid and tenidap as cyclo-oxygenase inhibitors were markedly reduced in blood (IC50 = 6.5 and 10 microM respectively) and neither significantly inhibited 5-lipoxygenase. Since both drugs also failed to inhibit 5-lipoxygenase in rat blood ex vivo, we conclude that, at physiological levels of plasma proteins, tolfenamic acid and tenidap are selective cyclo-oxygenase inhibitors.
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