氮䓬斯汀
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临床资料 | |
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商品名 | Astelin、Optivar、Allergodil及其他[1] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a603009 |
核准状况 | |
怀孕分级 |
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给药途径 | 眼部给药、鼻喷雾、口服 |
ATC码 | |
法律规范状态 | |
法律规范 |
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药物动力学数据 | |
生物利用度 | 40%(经鼻)[3] |
代谢产物 | 去甲基氮䓬斯汀(活性成分)[3] |
药效起始时间 | 1小时内[3] |
生物半衰期 | 22小时[3] |
作用时间 | 12小时[3] |
识别信息 | |
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CAS号 | 58581-89-8 ![]() 79307-93-0 |
PubChem CID | |
IUPHAR/BPS | |
DrugBank |
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ChemSpider | |
UNII |
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KEGG | |
ChEBI |
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ChEMBL |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.133.278 |
化学信息 | |
化学式 | C22H24ClN3O |
摩尔质量 | 381.90 g·mol−1 |
3D模型(JSmol) | |
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氮䓬斯汀[注 1](英语:Azelastine)是一种H1受体拮抗剂,在英文中其商品名有Optivar等,多用作鼻喷剂以治疗过敏性鼻炎,或作滴眼液以治疗过敏性结膜炎;[4][5]其他用途包括治疗哮喘、皮疹等,此时通过口服用药。[6]此药物通过眼部给药时在一分钟内起效,通过鼻腔给药则一小时内起效,[7]其效力可持续至十二小时。[7]
本药物常见的不良反应包括头痛、嗜睡、味觉改变、咽喉痛等;[7]至于孕期或哺乳中使用是否安全,则尚不明确。[8]作为第二代抗组胺药,本药物能阻挡包括组胺在内的多种炎症介质释放,以发挥作用。[6][7]
氮䓬斯汀在1971年获得专利,1986年应用于医药。[9]在美国,其有仿制药面市。[2] 2020年,本药物为美国处方中第173常见者,超过三百万张处方开出本药。[10][11]
医疗用途
氮䓬斯汀鼻喷雾剂可用于局部治疗季节性过敏性鼻炎及常年性过敏性鼻炎的症状,如流涕不止、喷嚏、鼻痒等,五岁及以上人群均可使用;[12][13][14]在某些国家,还可用于治疗血管运动性鼻炎,适用于十二岁及以上的人群。[14]氮䓬斯汀滴眼液则可用于局部治疗季节性及常年性的过敏性结膜炎。[15][16]
不良反应
于患有过敏性鼻炎的人群而言,氮䓬斯汀安全且耐受性好,不论成人儿童皆然。[17][18][19]口苦、头痛、鼻腔灼痛、嗜睡为最常报道的不良反应实例。美国的处方建议中则警告不得同时使用酒精及/或其他中枢神经系统抑制剂;一些晚近的研究[20][21]表明本药物导致嗜睡的比例(约2%)同安慰剂相似。
最常见的不良反应是口中发苦(人群中20%左右),有鉴于此,生产商另有制造添加三氯蔗糖的氮䓬斯汀制剂。[22]口苦的问题通过正确运用鼻喷雾(即头部略前倾,勿将药物吸入过深处)或可减轻,换用氮䓬斯汀/三氯蔗糖制剂也可。[23]
再者,使用鼻喷雾的抗组胺药时可能失嗅,氮䓬斯汀制剂无论是否添加三氯蔗糖,都存在此类风险。[7]
药理学
药物动力学
氮䓬斯汀之起效有三重方式:[24]
药代动力学
通过鼻腔给药时,氮䓬斯汀在全身的生物利用度大约40%;[3]二至三小时内,测得最大血药浓度(Cmax)。[3]本药物的生物半衰期、稳态分布体积及血浆清除率分别为22 h、14.5 L·kg-1、0.5 L·h-1·kg-1(基于静脉给药及口服给药数据)。口服剂量中约75%通过排遗排出。经口服给药的氮䓬斯汀,其药代动力学不受年龄、性别或肝损伤情况影响。[24]
代谢情况
氮䓬斯汀经细胞色素P450酶超家族而氧化代谢成具有活性的代谢产物去甲基氮䓬斯汀,另有两种无活性的羧酸代谢产物。[24]
化学性状
盐酸氮䓬斯汀的化学命名为(±)-1-(2H)-二氮杂萘酮, 4-[(4-氯苄基) 甲基]-2-(六氢-1-甲基-1H-氮杂䓬-4-基)-盐酸盐,呈白色状,基本无臭,味苦。[25]
注释
- ^ 常作“氮卓斯汀”。
参考文献
- ^ international listings for azelastine. Drugs.com. [2015-06-28]. (原始内容存档于2016-06-05).
- ^ 2.0 2.1 FDA Approves a Nasal Antihistamine for Nonprescription Use. U.S. Food and Drug Administration (FDA) (新闻稿). 2021-06-17 [2021-06-21]. (原始内容存档于2023-10-01).
- ^ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Lieberman P, Hernandez-Trujillo V, Lieberman J, Frew AJ. Antihistamines. Clinical Immunology. Elsevier. 2008: 1317–1329. ISBN 9780323044042. doi:10.1016/b978-0-323-04404-2.10089-2.
经过鼻腔给药后,其在全身的生物利用度约为40%。氮䓬斯汀于给药后第一个小时内发挥效力,给药后一至三小时达到效果峰值。起效时间在十二小时左右。鼻腔给药所得结果为二至三小时内达到最大血药浓度。……原化合物的半衰期为二十二小时……
After intranasal administration, its systemic bioavailability is approximately 40%. Azelastine has an onset of action within the first hour of administration and reaches peak activity at 1–3 hours after administration. Duration of activity is about 12 hours. Intranasal administration results in maximal plasma concentrations in 2–3 hours. ... The half-life of the parent compound is 22 hours ... - ^ British national formulary : BNF 76 76. Pharmaceutical Press. 2018: 1169. ISBN 9780857113382.
- ^ Al-Ahmad M, Hassab M, Al Ansari A. Allergic and Non-allergic Rhinitis. Textbook of Clinical Otolaryngology. Cham: Springer International Publishing. 2020-12-21: 241–252. ISBN 978-3-030-54087-6. S2CID 234142758. doi:10.1007/978-3-030-54088-3_22.
经鼻用药的H1受体拮抗剂如氮䓬斯汀等对控制鼻腔症状有效果,一日需使用两次。
Intranasal H1 antihistamines such as azelastine are effective for controlling nasal symptoms. They need to be applied twice daily. - ^ 6.0 6.1 Aronson JK. Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. 2015: 782. ISBN 9780444537164.
- ^ 7.0 7.1 7.2 7.3 7.4 Azelastine Hydrochloride Monograph for Professionals. Drugs.com. American Society of Health-System Pharmacists. [2023-07-09]. (原始内容存档于2019-03-26).
- ^ Azelastine ophthalmic (Optivar) Use During Pregnancy. Drugs.com. [2019-03-26]. (原始内容存档于2019-03-26).
- ^ Fischer J, Ganellin CR. Analogue-based Drug Discovery. John Wiley & Sons. 2006: 548 [2023-07-09]. ISBN 9783527607495. (原始内容存档于2023-01-10).
- ^ The Top 300 of 2020. ClinCalc. [2022-10-07]. (原始内容存档于2020-05-14).
- ^ Azelastine - Drug Usage Statistics. ClinCalc. [2022-10-07]. (原始内容存档于2023-07-09).
- ^ Allergic Rhinitis and its Impact on Asthma (ARIA) treatment guidelines. AHRQ. (原始内容存档于2013-02-18).
- ^ Rhinolast Nasal Spray Summary of Product Characteristics. 2009-10 [2010-04-27]. (原始内容存档于2011-01-03).
- ^ 14.0 14.1 Astelin- azelastine hydrochloride spray, metered. [2023-07-09]. (原始内容存档于2023-07-09).
- ^ Optilast Eye Drops Summary of Product Characteristics. 2010-01 [2010-04-27]. (原始内容存档于2011-01-03).
- ^ Optivar- azelastine hydrochloride solution/ drops. [2023-07-09]. (原始内容存档于2021-06-24).
- ^ McNeely W, Wiseman LR. Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis. Drugs. 1998-07, 56 (1): 91–114. PMID 9664202. S2CID 46956783. doi:10.2165/00003495-199856010-00011.
- ^ Ratner PH, Findlay SR, Hampel F, van Bavel J, Widlitz MD, Freitag JJ. A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis. The Journal of Allergy and Clinical Immunology. 1994-11, 94 (5): 818–25. PMID 7963150. doi:10.1016/0091-6749(94)90148-1.
- ^ LaForce C, Dockhorn RJ, Prenner BM, et al. Safety and efficacy of azelastine nasal spray (Astelin NS) for seasonal allergic rhinitis: a 4-week comparative multicenter trial. Annals of Allergy, Asthma & Immunology. 1996-02, 76 (2): 181–8. PMID 8595539. doi:10.1016/S1081-1206(10)63420-5.
- ^ Corren J, Storms W, Bernstein J, Berger W, Nayak A, Sacks H. Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis. Clinical Therapeutics. 2005-05, 27 (5): 543–53. PMID 15978303. doi:10.1016/j.clinthera.2005.04.012.
- ^ Berger W, Hampel F, Bernstein J, Shah S, Sacks H, Meltzer EO. Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis. Annals of Allergy, Asthma & Immunology. 2006-09, 97 (3): 375–81. PMID 17042145. doi:10.1016/S1081-1206(10)60804-6.
- ^ Kalpaklioglu AF, Kavut AB. Comparison of azelastine versus triamcinolone nasal spray in allergic and nonallergic rhinitis. American Journal of Rhinology & Allergy. 2010, 24 (1): 29–33. PMID 20109317. S2CID 24449860. doi:10.2500/ajra.2010.24.3423.
- ^ Bernstein JA. Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Current Medical Research and Opinion. 2007-10, 23 (10): 2441–52. PMID 17723160. S2CID 25827650. doi:10.1185/030079907X226302.
- ^ 24.0 24.1 24.2 Horak F, Zieglmayer UP. Azelastine nasal spray for the treatment of allergic and nonallergic rhinitis. Expert Review of Clinical Immunology. 2009-11, 5 (6): 659–669. PMID 20477689. S2CID 32512061. doi:10.1586/eci.09.38.
- ^ Azelastine. Drugs.com. [2015-06-28]. (原始内容存档于2016-08-20).
外部链接
- Azelastine. Drug Information Portal. U.S. National Library of Medicine. [2023-07-09]. (原始内容存档于2022-09-26).
- Azelastine hydrochloride. Drug Information Portal. U.S. National Library of Medicine. [2023-07-09]. (原始内容存档于2022-09-24).
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