Orally administered tolfenamic acid inhibits leukotriene synthesis in isolated human peripheral polymorphonuclear leukocytes.
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.
Moilanen
E
E
Department of Biomedical Sciences, University of Tampere, Finland.
Alanko
J
J
Juhakoski
A
A
Vapaatalo
H
H
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000097:blood; D062367:ortho-Aminobenzoates / Q000493:pharmacokinetics / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013189:SRS-A; D062367:ortho-Aminobenzoates; D007975:Leukotriene B4; D000001:Calcimycin; C009500:tolfenamic acid; D013929:Thromboxane B2