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Can urinary eicosanoids be a potential predictive marker of clinical response to thromboxane A2 receptor antagonist in asthmatic patients?
Respir Med. 1999 Dec; 93(12):891-7.RM

Abstract

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.

Authors+Show Affiliations

Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study

Language

eng

PubMed ID

10653051

Citation

Tanaka, H, et al. "Can Urinary Eicosanoids Be a Potential Predictive Marker of Clinical Response to Thromboxane A2 Receptor Antagonist in Asthmatic Patients?" Respiratory Medicine, vol. 93, no. 12, 1999, pp. 891-7.
Tanaka H, Igarashi T, Saitoh T, et al. Can urinary eicosanoids be a potential predictive marker of clinical response to thromboxane A2 receptor antagonist in asthmatic patients? Respir Med. 1999;93(12):891-7.
Tanaka, H., Igarashi, T., Saitoh, T., Teramoto, S., Miyazaki, N., Kaneko, S., Ohmichi, M., & Abe, S. (1999). Can urinary eicosanoids be a potential predictive marker of clinical response to thromboxane A2 receptor antagonist in asthmatic patients? Respiratory Medicine, 93(12), 891-7.
Tanaka H, et al. Can Urinary Eicosanoids Be a Potential Predictive Marker of Clinical Response to Thromboxane A2 Receptor Antagonist in Asthmatic Patients. Respir Med. 1999;93(12):891-7. PubMed PMID: 10653051.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Can urinary eicosanoids be a potential predictive marker of clinical response to thromboxane A2 receptor antagonist in asthmatic patients? AU - Tanaka,H, AU - Igarashi,T, AU - Saitoh,T, AU - Teramoto,S, AU - Miyazaki,N, AU - Kaneko,S, AU - Ohmichi,M, AU - Abe,S, PY - 2000/2/1/pubmed PY - 2000/2/1/medline PY - 2000/2/1/entrez SP - 891 EP - 7 JF - Respiratory medicine JO - Respir Med VL - 93 IS - 12 N2 - 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. SN - 0954-6111 UR - https://www.unboundmedicine.com/medline/citation/10653051/Can_urinary_eicosanoids_be_a_potential_predictive_marker_of_clinical_response_to_thromboxane_A2_receptor_antagonist_in_asthmatic_patients L2 - https://linkinghub.elsevier.com/retrieve/pii/S0954-6111(99)90055-0 DB - PRIME DP - Unbound Medicine ER -