酮替酚

**酮替酚**
臨床資料
商品名（英语：Drug nomenclature）	Zaditor
AHFS/Drugs.com	Monograph
MedlinePlus	a604033
懷孕分級	澳: B1 ; ;
给药途径	By mouth (tablets), topical eye drops
ATC碼	R06AX17 (WHO) S01GX08;
法律規範狀態
法律規範	美：Oral — withdrawn, was Rx-only; Eye drops — over-the-counter;
藥物動力學數據
生物利用度	60%
血漿蛋白結合率	75%
药物代谢	Hepatic
生物半衰期	12 hours
识别信息
	IUPAC命名法 4-(1-Methylpiperidin-4-ylidene)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one; ;
CAS号	34580-14-8
PubChem CID	3827;
IUPHAR/BPS	7206;
DrugBank	DB00920 ;
ChemSpider	3695 ;
UNII	HBD503WORO;
KEGG	D01332 ;
ChEBI	CHEBI:92511;
ChEMBL	ChEMBL534 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID7023190 ;
ECHA InfoCard	100.047.348
化学信息
化学式	C19H19NOS
摩尔质量	309.43 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C3c1sccc1C(\c2c(cccc2)C3)=C4/CCN(C)CC4;
	InChI InChI=1S/C19H19NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11H,6-7,9-10,12H2,1H3 ; Key:ZCVMWBYGMWKGHF-UHFFFAOYSA-N ;

酮替酚，商品名包括Zaditor等，是第二代非竞争性 H₁抗组胺药和肥大细胞稳定剂，常见的酮替酚药物一般为其富马酸盐（富马酸酮替酚）。酮替酚有两种给药途径。眼部给药时用于治疗过敏性结膜炎^[1]，口服给药时用于预防哮喘发作、过敏反应及各种过敏性肥大细胞疾病。 ^[2] ^[3] ^[4]^[5]

酮替酚于 1970 年获得专利，并于 1976 年投入医疗使用。 ^[6]

医疗用途[编辑]

酮替芬可用于缓解和预防大多数季节性过敏相关的眼部瘙痒和刺激，起效时间约在给药后几分钟内，其药物代谢半衰期约为 12 小时。该药物尚未在三岁以下儿童中进行过研究。 ^[1] ^[7]除了抗组胺活性外，它还是一种功能性白三烯拮抗剂^[8]和磷酸二酯酶抑制剂。 ^[9]

口服酮替酚在加拿大、欧洲和墨西哥已用于治疗哮喘、过敏性鼻炎、过敏性结膜炎、特应性皮炎、慢性荨麻疹、寒冷性荨麻疹、胆碱能性荨麻疹，以及包括肥大细胞增多症、肥大细胞活化综合征 (MCAS)、过敏性和非过敏性过敏反应、血管性水肿和食物过敏在内的系统性肥大细胞疾病。

在美国，酮替酚可凭处方购买。对于患哮喘或过敏性疾病的成人及年龄较大的儿童，酮替芬的推荐剂量为1毫克/次，每天两次。对于治疗荨麻疹相关的用途，FDA 工作人员建议进行更广泛的评估。^[4]^[5]

该药品还可能有助于缓解肠易激综合征。 ^[10]

副作用[编辑]

全身性给药（口服）的副作用包括嗜睡、体重增加（5千克左右）、口干、易怒和鼻出血增加等。 ^[11]^{[來源可靠？]}

药理[编辑]

酮替芬是一种选择性抗组胺药（即 H₁ 组胺受体的反激动剂）(K _i = 0.166 nM) ^[12] 和肥大细胞稳定剂。 ^[13]此外，酮替芬有较弱的抗胆碱能（K _i = 204 nM 对于mACh ) 和抗血清素(K _i = 38.9 nM 对于 5-HT_2A ) 活性。 ^[12] ^[14]然而在常用临床剂量下，酮替芬的抗胆碱能和抗血清素活性均不显著。 ^[15]

社会与文化[编辑]

商品名[编辑]

酮替芬在全球以许多不同商品名销售。 ^[16]

参考[编辑]

^ ^1.0 ^1.1 ^1.2 Zaditor- ketotifen fumarate solution. DailyMed. 13 February 2020 [4 September 2020]. （原始内容存档于2021-06-11）. 引证错误：带有name属性“Zaditor_pi”的<ref>标签用不同内容定义了多次
^ Sokol, Kristin C.; Amar, Neil K.; Starkey, Jonathan; Grant, J. Andrew. Ketotifen in the management of chronic urticaria: Resurrection of an old drug. Annals of Allergy, Asthma & Immunology. 2013, 111 (6): 433–6. PMC 4309375 . PMID 24267353. doi:10.1016/j.anai.2013.10.003.
^ Shawky, Rabah M.; Seifeldin, Neveen S. The relation between antihistamine medication during early pregnancy & birth defects. Egyptian Journal of Medical Human Genetics. 2015, 16 (4): 287–90. doi:10.1016/j.ejmhg.2015.04.003.
^ ^4.0 ^4.1 Zuberbier, Torsten. A Summary of the New International EAACI/GA2LEN/EDF/ WAO Guidelines in Urticaria. World Allergy Organization Journal. 2012, 5 (1): S1–S5. PMC 3488932 . PMID 23268477. doi:10.1186/1939-4551-5-S1-S1.
^ ^5.0 ^5.1 Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau AM, Grattan CE, Kapp A, Maurer M, Merk HF, Rogala B, Saini S, Sánchez-Borges M, Schmid-Grendelmeier P, Schünemann H, Staubach P, Vena GA, Wedi B. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy. October 2009, 64 (10): 1427–1443. PMID 19772513. S2CID 14587946. doi:10.1111/j.1398-9995.2009.02178.x.
^ Fischer, Jnos; Ganellin, C. Robin. Analogue-based Drug Discovery. John Wiley & Sons. 2006: 548 [2022-03-19]. ISBN 9783527607495. （原始内容存档于2020-08-13）.
^ Grahnén, A.; Lönnebo, A.; Beck, O.; Eckernäs, S-Å; Dahlström, B.; Lindström, B. Pharmacokinetics of ketotiffn after oral administration to healthy male subjects. Biopharmaceutics & Drug Disposition. 1992, 13 (4): 255–62. PMID 1600111. doi:10.1002/bdd.2510130404.
^ Fink, A.; Bibi, H.; Eliraz, A.; Schlesinger, M.; Bentwich, Z. Ketotifen, disodium cromoglycate, and verapamil inhibit leukotriene activity: determination by tube leukocyte adherence inhibition assay. Annals of Allergy. 1986, 57 (2): 103–106 [2022-03-19]. ISSN 0003-4738. PMID 3090908. （原始内容存档于2021-06-11）.
^ Castillo, J. G.; Gamboa, P. M.; García, B. E.; Oehling, A. Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergologia Et Immunopathologia. 1990, 18 (4): 197–201 [2022-03-19]. ISSN 0301-0546. PMID 1702263. （原始内容存档于2021-06-11）.
^ Klooker, T. K.; Braak, B.; Koopman, K. E.; Welting, O.; Wouters, M. M.; Van Der Heide, S.; Schemann, M.; Bischoff, S. C.; Van Den Wijngaard, R. M. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome (PDF). Gut. 2010, 59 (9): 1213–21 [2022-03-19]. PMID 20650926. doi:10.1136/gut.2010.213108. （原始内容 (PDF)存档于2021-06-11）.
^ Zaditen - MIMS online. www.mims.co.uk. [2022-03-19]. （原始内容存档于2020-10-25）.
^ ^12.0 ^12.1 Studies on the novel antiallergic agent HSR-609: its penetration into the central nervous system in mice and guinea pigs and its selectivity for the histamine H1-receptor. Jpn. J. Pharmacol. 1997, 73 (4): 291–8. PMID 9165365. doi:10.1254/jjp.73.291.
^ Thomas L. Lemke; David A. Williams. Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. 2008: 1019– [2022-03-19]. ISBN 978-0-7817-6879-5. （原始内容存档于2021-06-11）.
^ V Alagarsamy. Textbook of Medicinal Chemistry Vol II - E-Book. Elsevier Health Sciences. 16 June 2012: 38– [2022-03-19]. ISBN 978-81-312-3259-0. （原始内容存档于2021-06-20）.
^ Jürgen Drews. Immunopharmacology: Principles and Perspectives. Springer Science & Business Media. 6 December 2012: 282– [2022-03-19]. ISBN 978-3-642-75561-3. （原始内容存档于2021-06-18）.
^ Ketotifen International. Drugs.com. [4 September 2020]. （原始内容存档于2021-04-11）.

外部链接[编辑]

Ketotifen. Drug Information Portal. U.S. National Library of Medicine. [2022-03-19]. （原始内容存档于2022-03-19）.

#invoke:navbox Template:Tricyclics

[Zaditor_pi-1] 1.0 ^1.1 ^1.2 Zaditor- ketotifen fumarate solution. DailyMed. 13 February 2020 [4 September 2020]. （原始内容存档于2021-06-11）. 引证错误：带有name属性“Zaditor_pi”的<ref>标签用不同内容定义了多次

[2] Sokol, Kristin C.; Amar, Neil K.; Starkey, Jonathan; Grant, J. Andrew. Ketotifen in the management of chronic urticaria: Resurrection of an old drug. Annals of Allergy, Asthma & Immunology. 2013, 111 (6): 433–6. PMC 4309375 . PMID 24267353. doi:10.1016/j.anai.2013.10.003.

[3] Shawky, Rabah M.; Seifeldin, Neveen S. The relation between antihistamine medication during early pregnancy & birth defects. Egyptian Journal of Medical Human Genetics. 2015, 16 (4): 287–90. doi:10.1016/j.ejmhg.2015.04.003.

[Zuberbier2012-4] 4.0 ^4.1 Zuberbier, Torsten. A Summary of the New International EAACI/GA2LEN/EDF/ WAO Guidelines in Urticaria. World Allergy Organization Journal. 2012, 5 (1): S1–S5. PMC 3488932 . PMID 23268477. doi:10.1186/1939-4551-5-S1-S1.

[Zuberbier_et_al_2009-5] 5.0 ^5.1 Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau AM, Grattan CE, Kapp A, Maurer M, Merk HF, Rogala B, Saini S, Sánchez-Borges M, Schmid-Grendelmeier P, Schünemann H, Staubach P, Vena GA, Wedi B. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy. October 2009, 64 (10): 1427–1443. PMID 19772513. S2CID 14587946. doi:10.1111/j.1398-9995.2009.02178.x.

[Fis2006-6] Fischer, Jnos; Ganellin, C. Robin. Analogue-based Drug Discovery. John Wiley & Sons. 2006: 548 [2022-03-19]. ISBN 9783527607495. （原始内容存档于2020-08-13）.

[7] Grahnén, A.; Lönnebo, A.; Beck, O.; Eckernäs, S-Å; Dahlström, B.; Lindström, B. Pharmacokinetics of ketotiffn after oral administration to healthy male subjects. Biopharmaceutics & Drug Disposition. 1992, 13 (4): 255–62. PMID 1600111. doi:10.1002/bdd.2510130404.

[8] Fink, A.; Bibi, H.; Eliraz, A.; Schlesinger, M.; Bentwich, Z. Ketotifen, disodium cromoglycate, and verapamil inhibit leukotriene activity: determination by tube leukocyte adherence inhibition assay. Annals of Allergy. 1986, 57 (2): 103–106 [2022-03-19]. ISSN 0003-4738. PMID 3090908. （原始内容存档于2021-06-11）.

[9] Castillo, J. G.; Gamboa, P. M.; García, B. E.; Oehling, A. Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergologia Et Immunopathologia. 1990, 18 (4): 197–201 [2022-03-19]. ISSN 0301-0546. PMID 1702263. （原始内容存档于2021-06-11）.

[10] Klooker, T. K.; Braak, B.; Koopman, K. E.; Welting, O.; Wouters, M. M.; Van Der Heide, S.; Schemann, M.; Bischoff, S. C.; Van Den Wijngaard, R. M. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome (PDF). Gut. 2010, 59 (9): 1213–21 [2022-03-19]. PMID 20650926. doi:10.1136/gut.2010.213108. （原始内容 (PDF)存档于2021-06-11）.

[11] Zaditen - MIMS online. www.mims.co.uk. [2022-03-19]. （原始内容存档于2020-10-25）.

[pmid9165365-12] 12.0 ^12.1 Studies on the novel antiallergic agent HSR-609: its penetration into the central nervous system in mice and guinea pigs and its selectivity for the histamine H1-receptor. Jpn. J. Pharmacol. 1997, 73 (4): 291–8. PMID 9165365. doi:10.1254/jjp.73.291.

[LemkeWilliams2008-13] Thomas L. Lemke; David A. Williams. Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. 2008: 1019– [2022-03-19]. ISBN 978-0-7817-6879-5. （原始内容存档于2021-06-11）.

[Alagarsamy2012-14] V Alagarsamy. Textbook of Medicinal Chemistry Vol II - E-Book. Elsevier Health Sciences. 16 June 2012: 38– [2022-03-19]. ISBN 978-81-312-3259-0. （原始内容存档于2021-06-20）.

[Drews2012-15] Jürgen Drews. Immunopharmacology: Principles and Perspectives. Springer Science & Business Media. 6 December 2012: 282– [2022-03-19]. ISBN 978-3-642-75561-3. （原始内容存档于2021-06-18）.

[16] Ketotifen International. Drugs.com. [4 September 2020]. （原始内容存档于2021-04-11）.

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