Chemistry:Seratrodast
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| Trade names | Bronica in Japan, Changnuo, Mai Xu Jia, Quan Kang Nuo in China and as Seradair in India. .[1] |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | By mouth (tablets, granules) |
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| Pharmacokinetic data | |
| Protein binding | >96% |
| Elimination half-life | 22 hours |
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| Formula | C22H26O4 |
| Molar mass | 354.446 g·mol−1 |
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Seratrodast (development name, AA-2414; marketed originally as Bronica)[2] is a thromboxane A2 (TXA2) receptor (TP receptor) antagonist used primarily in the treatment of asthma.[3][4] It was the first TP receptor antagonist that was developed as an anti-asthmatic drug and received marketing approval in Japan in 1997.[5] As of 2017 seratrodast was marketed as Bronica in Japan, and as Changnuo, Mai Xu Jia, Quan Kang Nuo in China.[1]
Unlike thromboxane synthase inhibitors such as ozagrel, seratrodast does not affect thrombus formation, time to occlusion and bleeding time.[6] Seratrodast has no effect on prothrombin time and activated partial thromboplastin time, thus ruling out any action on blood coagulation cascade.[7]
Medical uses
Seratrodast is used to treat asthma.[8][9]
There are no adequate and well-controlled studies of seratrodast in pregnant women. The drug should be used in pregnancy only if the potential benefits justify the risk to the fetus.[9] Seratrodast should not be used during lactation.[9]
The safety and efficacy of seratrodast has not been established in children (<18 years of age).[9]
Contraindications and interactions
Seratrodast should not be used in people with liver disease.[9]
Use with paracetamol or with cephem antibiotics increases the risk of liver damage. Use with aspirin increases the bioavailability of seratrodast.[9]
Adverse effects
The most frequently observed (0.1 to 5%) adverse reactions include elevated transaminases, nausea, loss of appetite, stomach discomfort, abdominal pain, diarrhea, constipation, dry mouth, taste disturbance, drowsiness, headache, dizziness, palpitations and malaise.[9] Less than 0.1% of patients experienced vomiting, thrombocytopenia, epistaxis, bleeding tendency, insomnia, tremor, numbness, hot flushes and edema.[9] All the adverse reactions reported were of mild to moderate severity, and resolved when the drug was discontinued.[9]
Pharmacology
Thromboxane A2 (TXA2) is generated in the lungs of people with asthma, and when it signals through the thromboxane receptor it causes bronchoconstriction, vasoconstriction, mucous secretion, and airway hyper-responsiveness. Seratrodast inhibits the activity of the thromboxane receptor, blocking the effects of TXA2.[10]
Pharmacokinetics
The pharmacokinetics of seratrodast have been studied in Japanese and Caucasian, including Indian, healthy volunteers.[11][12][13][14] The plasma concentrations of seratrodast increase with increasing doses. The absorption of seratrodast is relatively rapid with maximum plasma concentrations of 4.6–6 μg/ml obtained in 3 to 4 hours.[11] Steady state plasma concentrations of seratrodast are reached within 4–5 days.[13] Seratrodast is slowly cleared, mainly by hepatic biotransformation. The drug shows biexponential decay in plasma profiles with a mean elimination half-life of 22 hours.[11][13] Approximately 20% of the administered dose is recovered in the urine, with 60% of the urinary recovery being in the form of conjugates [12]
Chemistry
Seratrodast can be prepared in five steps starting from pimelic acid monoester.[15]
History
Seratrodast was the first thromboxane receptor antagonist to reach the market as a treatment for asthma; it was approved in Japan in 1997.[8]
Society and culture
As of 2017 seratrodast was marketed as Bronica in Japan, Changnuo, Mai Xu Jia, Quan Kang Nuo in China and as Seretra & Seradair in India.[1]
Research
Seratrodast was studied in perennial allergic rhinitis, chronic bronchitis and chronic pulmonary emphysema but efforts to bring the drug to market in those indications was abandoned around 2000.[2]
References
- ↑ 1.0 1.1 1.2 "Seratrodast international brands". Drugs.com. https://www.drugs.com/international/seratrodast.html.
- ↑ 2.0 2.1 "Seratrodast" (in en). AdisInsight. http://adisinsight.springer.com/drugs/800000083.
- ↑ "[Thromboxane A2 receptor antagonist in asthma therapy]" (in ja). Nihon Rinsho. Japanese Journal of Clinical Medicine 54 (11): 3045–8. November 1996. PMID 8950952.
- ↑ "[Study on the inhibitory effect of AA-2414 on platelet aggregation and its clinical effect in asthmatic patients]" (in ja). Arerugi [Allergy] 42 (1): 18–25. January 1993. PMID 8457165.
- ↑ "Thromboxane A2 inhibition: therapeutic potential in bronchial asthma". American Journal of Respiratory Medicine 1 (1): 11–7. 2002. doi:10.1007/bf03257158. PMID 14720071.
- ↑ "Pharmacological characterization of N-tert-butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a novel thromboxane A2 receptor antagonist and thromboxane synthase inhibitor in a rat model of arterial thrombosis and its effects on bleeding time". The Journal of Pharmacology and Experimental Therapeutics 309 (2): 498–505. May 2004. doi:10.1124/jpet.103.063610. PMID 14742735.
- ↑ "Seratrodast (AA-2414)—A Novel Thromboxane-A2 Receptor Antagonist". Cardiovascular Drug Reviews 14 (3): 272–85. 1996. doi:10.1111/j.1527-3466.1996.tb00231.x.
- ↑ 8.0 8.1 "Prostanoids as pharmacological targets in COPD and asthma". European Journal of Pharmacology 533 (1–3): 89–100. March 2006. doi:10.1016/j.ejphar.2005.12.058. PMID 16458293.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 "医療用医薬品 : ブロニカ (Japanese label)" (in ja). KEGG. October 2016. http://www.kegg.jp/medicus-bin/japic_med?japic_code=00002634.
- ↑ "Therapeutic potential of thromboxane inhibitors in asthma". Expert Opinion on Investigational Drugs 11 (2): 275–81. February 2002. doi:10.1517/13543784.11.2.275. PMID 11829716.
- ↑ 11.0 11.1 11.2 An open-labeled, randomized, cross-over bioequivalence study of Seratrodast 80mg under fasting condition. Data on file (appears on website on Seretra)
- ↑ 12.0 12.1 "The clinical phase I study of AA-2414, a thromboxane A, receptor antagonist – repeated-dose study at 160 mg once daily for 7 days". Clin Pharmacol 9 (Suppl. 8): 41–55. 1993.
- ↑ 13.0 13.1 13.2 "Characterization of the pharmacokinetics and pharmacodynamics of a new oral thromboxane A2-receptor antagonist AA-2414 in normal subjects: population analysis". Clinical Pharmacology and Therapeutics 55 (4): 441–50. April 1994. doi:10.1038/clpt.1994.54. PMID 8162671.
- ↑ "Single-dose and steady-state pharmacokinetics of seratrodast in healthy male and female volunteers". Pharm Res 13 (Suppl. 9). 1996.
- ↑ "Quinones. 4. Novel eicosanoid antagonists: synthesis and pharmacological evaluation". Journal of Medicinal Chemistry 32 (9): 2214–21. September 1989. doi:10.1021/jm00129a030. PMID 2769691.
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