Can urinary eicosanoids be a potential predictive marker of clinical response to thromboxane A2 receptor antagonist in asthmatic patients?
Thromboxane (TX) A2 is an important bronchoconstrictor in the pathogenesis of asthma. Seratrodast, known as AA-2414, is a new oral TXA2 receptor antagonist which is currently prescribed in asthma therapy in Japan. However its clinical effects have been very different in individual subjects. To assess whether the clinical efficacy of TXA2 antagonist is predictable on the basis of urinary arachidonic acid metabolites in urine of patients with asthma, an open and multicentre trial was conducted. Fifty adult asthmatic subjects (women/men = 28/22) were enrolled [resting mean forced expiratory volume in 1 sec (FEV1)% was 82%; range, 50-96%]. Urinary levels of 11-dehydro-TXB2, leukotriene (LT) E4, 2,3-dinor-6-keto-prostaglandin F1alpha and creatinine in 3-h urine collected in the morning at the start of seratrodast (80 mg day(-1), once a day at evening for 4 weeks) were measured. Responders were defined by improvements of asthma symptoms score and peak expiratory flow rate (PEFR). Of the 50 subjects, 45 completed this study. Eighteen patients were responders and the other 27 were nonresponders. There were no significant differences between the two groups in patients' characteristics, baseline lung functions, treatments and baseline urinary eicosanoids. The 11-dehydro-TXB2/LTE4 ratio of responders was significantly higher (P = 0.0091) than that of non-responders (mean +/- SE, 7.49+/-0.71 vs. 5.09+/-0.67). Eleven patients out of 18 responders agreed to continue this drug for 6 months, the 11-dehydro-TXB2/LTE4 ratio decreased during this period, but not significantly. Our data demonstrated that responders and non-responders to TXA2 receptor antagonist existed in patients with asthma, and it suggests that the ratio of urinary eicosanoids might be a possible predictor of the effects of TXA2 receptor antagonist.
Tanaka
H
H
Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Igarashi
T
T
Saitoh
T
T
Teramoto
S
S
Miyazaki
N
N
Kaneko
S
S
Ohmichi
M
M
Abe
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D016227:Benzoquinones / Q000627:therapeutic use*; D003404:Creatinine / Q000652:urine; D015777:Eicosanoids / Q000652:urine*; D005260:Female; D005541:Forced Expiratory Volume; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D018927:Anti-Asthmatic Agents; D016227:Benzoquinones; D015777:Eicosanoids; D006538:Heptanoic Acids; D017482:Receptors, Thromboxane; C060230:seratrodast; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D003404:Creatinine