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Orally administered tolfenamic acid inhibits leukotriene synthesis in isolated human peripheral polymorphonuclear leukocytes

  • Inflammation and Immunomodulation
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Abstract

Special interest has been focused on the development of dual inhibitors of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism. In contrast to other classic NSAIDs, some fenamates in clinically achievable concentrations have been shown to inhibit synthesis of 5-lipoxygenase productsin vitro. In the present work, we studied the effect of orally administered tolfenamic acid (600 mg) on Ca ionophore A 23187-induced leukotriene synthesis in isolated human polymorphonuclear leukocytes. Leukotriene production was reduced in all 14 subjects studied, the mean inhibition of LTB4 synthesis being 16±3% and that of LTC4 33±7%. The inhibition correlated positively with serum tolfenamic acid concentrations. We suggest that inhibition of leukotriene synthesis is an additional mechanism of the anti-inflammatory, antimigraine and antidysmenorrhoeic effects of tolfenamic acid, and a possible explanation for its rare gastric and bronchoconstrictive side-effects.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Tampere, P.O. Box 607, 33101, Tampere

    E. Moilanen, J. Alanko & H. Vapaatalo

  2. Huhtamäki Oy Pharmaceuticals, Research Centre, P.O. Box 415, 20101, Turku, Finland

    A. Juhakoski

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  1. E. Moilanen
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  2. J. Alanko
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  3. A. Juhakoski
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  4. H. Vapaatalo
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Moilanen, E., Alanko, J., Juhakoski, A. et al. Orally administered tolfenamic acid inhibits leukotriene synthesis in isolated human peripheral polymorphonuclear leukocytes. Agents and Actions 28, 83–88 (1989). https://doi.org/10.1007/BF02022985

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