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Zileuton, a 5‐lipoxygenase inhibitor, increases production of thromboxane A 2 and platelet aggregation in patients with asthma
Author(s) -
Wu Xujun,
Dev Anil,
Leong Alfred Ba Tun
Publication year - 2003
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.10370
Subject(s) - zileuton , thromboxane b2 , platelet , thromboxanes , thromboxane , arachidonic acid , medicine , asthma , thromboxane a2 , platelet activation , leukotriene , pharmacology , thromboxane a synthase , cyclooxygenase , endocrinology , arachidonate 5 lipoxygenase , chemistry , biochemistry , enzyme
Leukotrienes, generated from arachidonic acid via the lipoxygenase pathway, play an important role in the pathophysiology of asthma. Therefore, leukotriene inhibitors, such as Zileuton, are used in the treatment of asthma. However, thromboxanes, generated from arachidonic acid via the cyclooxygenase pathway, play an important role in platelet aggregation and thrombosis. Therefore, we studied whether Zileuton, by shifting arachidonic acid to the cyclooxygenase pathway, enhances thromboxane production and, hence, platelet aggregation. Blood samples were collected from 10 asthmatic patients before and 2 weeks after standard Zileuton treatment. Spontaneous platelet aggregation was measured in platelet‐rich plasma. Platelet‐rich plasma was also used to determine thromboxane B 2 , a stable metabolite of thromboxane A 2 , as the indirect measure of thromboxane A 2 because thromboxane A 2 is too unstable for assay. Baseline thromboxane B 2 and platelet aggregation values in the 10 asthmatic patients were normal. Treatment with Zileuton for 2 weeks significantly increased thromboxane B 2 levels from baseline levels of 267 ± 54 μg/l to 389 ± 62 μg/l after 2 weeks of treatment ( P < 0.0002). Spontaneous platelet aggregation also increased significantly from baseline values of 4.2 ± 2.4% to 6.8 ± 2.8% after 2 weeks of treatment ( P < 0.0001). These results establish that Zileuton, an effective drug for asthma, adversely affects in vitro platelet function. The findings suggest that this drug, and perhaps related agents also, may pose a thrombotic risk; clinical attention will be needed to address this possibility. Am. J. Hematol. 74:23–25, 2003. © 2003 Wiley‐Liss, Inc.