Leukotrienes clinical significance

In a randomised, placebo-controlled study in 24 healthy subjects zileuton 800 mg every 12 hours was given with naproxen 500 mg every 12 hours for 5 days. No clinically significant change was found in the pharmacokinetics of either drug. Naproxen did not affect the inhibitory effect of zileuton on leukotriene B4 levels and similarly zileuton did not affect the inhibitory effect of naproxen on thromboxane B2. The inhibition of the 5-lipoxygenase pathway by zileuton did not appear to worsen the gastrointestinal effects associated with naproxen. No special precautions would seem necessary. ... 

The first SRS-A antagonist, FPL-55712 (26) (149), was discovered before the stmctures of the leukotrienes were detemiined. Although this compound is relatively weak as an antagonist and suffers from a very short half-life in vivo, it played an important role both in leukotriene stmcture elucidation and as a model for later antagonists. In work stmcturaHy related to FPL-55712, LY-171883 was developed (27) (150). LY-171883 was evaluated in several clinical trials before development was stopped. Orally adrninistered, LY-171883 blocked slightly the response to aerosol LTD improved pulmonary function (FEV ) in mild asthmatics (151), decreased the sensitivity of asthmatics to cold air-induced bronchoconstriction (152), and significantly reduced the bronchoconstrictor response to inhaled antigen (153). However, in all these studies the beneficial effects were minimal. 

Montelukast is a leukotriene receptor antagonist. It has been taken by about 2500 patients in over 40 clinical trials. Its adverse events have not been significantly different from those of placebo. 

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