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

• Published in: Agents and actions Vol. 28; no. 1-2; p. 83
• Main Authors: Moilanen, E, Alanko, J, Juhakoski, A, Vapaatalo, H
• Format: Journal Article
• Language: English
• Published: Switzerland 01.08.1989
• Subjects: Adult; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Calcimycin - pharmacology; Female; Humans; Leukotriene B4 - antagonists & inhibitors; Leukotriene B4 - biosynthesis; Male; Neutrophils - drug effects; Neutrophils - metabolism; ortho-Aminobenzoates - pharmacokinetics; ortho-Aminobenzoates - pharmacology; SRS-A - antagonists & inhibitors; SRS-A - biosynthesis; Thromboxane B2 - blood
• ISSN: 0065-4299
• DOI: 10.1007/BF02022985

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 products in 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 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.