Leukotriene (LT)-receptor antagonist is more effective in asthmatic patients with a low baseline ratio of urinary LTE4 to 2,3-dinor-6-keto-prostaglandin (PG)F1alpha.
BACKGROUND
To test the hypothesis that urinary levels of arachidonic acid metabolites may be a predicting factor of the effects of pranlukast, a selective leukotriene (LT) antagonist, on chronic adult asthma, we investigated the relationship between its clinical efficacy and urinary eicosanoid levels.


METHODS
An open, multicenter trial was conducted involving 38 stable moderate and severe asthmatic patients (mean percent predicted FEV1 was 71%). All patients received pranlukast (225 mg twice daily) for 4 weeks after a 2-week run-in period. Urinary levels of LTE4, 11-dehydro-thromboxane (TX) B2, 2,3-dinor-6-keto-prostaglandin (PG) F1alpha, and creatinine were measured in 3-h urine collected on day 1 of the treatment. The responder was defined by an improvement of asthma symptom scores and peak expiratory flow rate (PEFR).


RESULTS
One patient was excluded because of an adverse effect, nausea. Thirteen out of 37 subjects were responders and 24 were nonresponders. There were no significant differences in patients' backgrounds and urinary arachidonate levels between the two groups. The urinary LTE4 to 2,3-dinor-6-keto-PGF1alpha ratio in the responder was significantly lower (P=0.01) than that in the nonresponder. In all patients, a significant inverse correlation was revealed between the baseline urinary LTE4/2,3-dinor-6-keto-PGF1alpha ratio and the improvement of PEFR in the morning (r=-0.43, P=0.007).


CONCLUSIONS
These data suggested that the urinary ratio of LTE4 to 2,3-dinor-6-keto-PGF1alpha might be one of the predictive markers of the clinical efficacy of this LT-receptor antagonist in asthmatic subjects.
Tanaka
H
H
Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Saito
T
T
Kurokawa
K
K
Teramoto
S
S
Miyazaki
N
N
Kaneko
S
S
Hashimoto
M
M
Abe
S
S
D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D011460:Prostaglandins F / Q000652:urine*; D013929:Thromboxane B2 / Q000652:urine
D018927:Anti-Asthmatic Agents; D002867:Chromones; D020024:Leukotriene Antagonists; D011460:Prostaglandins F; D013929:Thromboxane B2; D017999:Leukotriene E4; C047681:pranlukast; C100006:prostaglandin F1