4-氨基水杨酸

**4-氨基水杨酸**
臨床資料
商品名（英语：Drug nomenclature）	Paser
懷孕分級	C;
给药途径	口服
ATC碼	J04AA01 (WHO) ;
法律規範狀態
法律規範	英：处方药（℞-only） (POM);
藥物動力學數據
血漿蛋白結合率	50–60%
药物代谢	肝脏
排泄途徑	肾脏
识别信息
	IUPAC命名法 4-amino-2-hydroxy-benzoic acid; ;
CAS号	65-49-6
PubChem CID	4649;
DrugBank	DB00233 ;
ChemSpider	4488 ;
UNII	5B2658E0N2;
KEGG	D00162 ;
ChEBI	CHEBI:27565 ;
ChEMBL	ChEMBL1169 ;
NIAID ChemDB	020064;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID2022591 ;
ECHA InfoCard	100.000.557
化学信息
化学式	C7H7NO3
摩尔质量	153.135 g/mol
3D模型（JSmol（英语：JSmol））	交互式图像;
熔点	150.5 °C（302.9 °F）
	SMILES O=C(O)c1ccc(cc1O)N;
	InChI InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11) ; Key:WUBBRNOQWQTFEX-UHFFFAOYSA-N ;

4-氨基水杨酸（英語：4-Aminosalicylic acid，又名对氨基水杨酸、氨基水杨酸或PAS）是一种用于治疗结核病的抗菌药。^[1] 它也被用于治疗炎症性肠病。^[2] 它通过抑制NF-κB及清除自由基而发挥作用。美沙拉嗪（5-氨基水杨酸）与4-氨基水杨酸十分相似，并同样具有药用。

加热后，4-氨基水杨酸会发生脱羧反应，分解成3-氨基苯酚和二氧化碳。^[3]

临床用途

目前，4-氨基水杨酸主要用于治疗结核病，但它也有其他用途。

结核病

1948年，4-氨基水杨酸开始被用于临床治疗结核病。它是链霉素之后人们发现的第二种能够治疗结核病的药物。在人们发现利福平与吡嗪酰胺之前，氨基水杨酸是治疗结核病的标配药物之一。^[4]

氨基水杨酸的疗效不如目前的五种抗结核病一线药物（异烟肼、利福平、乙胺丁醇、吡嗪酰胺、链霉素），并且价格相对较高，但仍在耐多药结核病的治疗中起着重要的作用。^[1] 它总是与其他抗结核药物一同使用。

氨基水杨酸治疗结核病是的剂量为150mg/kg/天，每天分2~4次服用；成年人通常每天分4次服用2~4克药物。服药时一般与酸性食物或饮料（如橙汁、苹果汁或番茄汁）一同服用。^[5] 目前氨基水杨酸在美国的商品则是Paser；市面上还曾经有过商品名为Pasinah^[6]或Pycamisan 33^[7]的氨基水杨酸与异烟肼组成的复方制剂。

炎症性肠病

自20世纪40年代起，4-氨基水杨酸也被用于治疗炎症性肠病，对其中的溃疡性结肠炎和克罗恩病效果较好；^[2] 但基本上已被柳氮磺胺吡啶和美沙拉嗪等药物所取代。

其它

4-氨基水杨酸也被研究用于锰中毒的螯合疗法，其中一项17年的随访研究显示它可能比其他常用的螯合剂（如EDTA）效果要好。^[8]

副作用

最常见的不良反应为胃肠道症状，这包括了恶心、呕吐和腹泻；缓释片能够帮助减轻这些副作用。^[9] 它还能够引起药源性肝炎。具有葡萄糖-6-磷酸脫氫酶缺乏症（蚕豆病）的患者应避免使用此药，否则将可能引起溶血。^[10] 甲状腺肿也有可能发生，因为氨基水杨酸能够抑制甲状腺激素的合成。^[11] 4-氨基水杨酸能够提升体内苯妥英的水平。与利福平合用的时候，后者的血药浓度将会降低约一半。^[12]

历史

4-氨基水杨酸是由瑞典化学家Jörgen Lehmann在研究结核杆菌对水杨酸的快速代谢时发现的。他在1944年第一次尝试使用口服氨基水杨酸治疗结核病——结果第一个接受治疗的病人的结核病奇迹般地被治愈了。^[13] 后来的研究显示，相对于之前发现的链霉素，这种药物没有耳毒性，且细菌不易对其产生抗药性。在1948年，英国医学研究委员会的研究者证实氨基水杨酸与链霉素的联合疗法比它们单用的效果要更好。^[1] 此后，结核病的治疗均采用多种药物的联合。

合成

4-氨基水杨酸是通过3-氨基苯酚的羧化合成的。^[14]

外部链接（英文）

Drugs.com（页面存档备份，存于互联网档案馆）
RxList

参考资料

^ ^1.0 ^1.1 ^1.2 W. Fox, G. A. Ellard, D. A. Mitchison. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. The International Journal of Tuberculosis and Lung Disease: The Official Journal of the International Union Against Tuberculosis and Lung Disease. 1999-10, 3 (10 Suppl 2): S231–279 [2019-02-12]. ISSN 1027-3719. PMID 10529902. （原始内容存档于2019-05-22）.
^ ^2.0 ^2.1 Daniel F, Seksik P, Cacheux W, Jian R, Marteau P. Tolerance of 4-aminosalicylic acid enemas in patients with inflammatory bowel disease and 5-aminosalicylic-induced acute pancreatitis. Inflamm Bowel Dis. 2004, 10 (3): 258–260. PMID 15290921. doi:10.1097/00054725-200405000-00013.
^ C. Vetuschi, G. Ragno, P. Mazzeo. Determination of p-aminosalicylic acid and m-aminophenol by derivative UV-spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis. 1988, 6 (4): 383–391 [2019-02-12]. ISSN 0731-7085. PMID 16867404. （原始内容存档于2019-05-22）.
^ Mitchison DA. Role of individual drugs in the chemotherapy of tuberculosis Role of individual drugs in the chemotherapy of tuberculosis. Int J Tuberc Lung Dis. 2000, 4 (9): 796–806. PMID 10985648.
^ Paser. RxList. [2008-10-10]. （原始内容存档于2008-10-25）.
^ Smith NP, Ryan TJ, Sanderson KV, Sarkany I. Lichen scrofulosorum: A report of four cases. Br J Dermatol. 1976, 94 (3): 319–325. PMID 1252363. doi:10.1111/j.1365-2133.1976.tb04391.x.
^ Black JM; Sutherland, IB. Two incidents of tuberculous infection by milk from attested herds. Br Med J. 1961, 1 (5241): 1732–1735. PMC 1954350 . PMID 20789163. doi:10.1136/bmj.1.5241.1732.
^ Yue-Ming Jiang, Xue-An Mo, Feng-Qi Du, Xue Fu, Xia-Yan Zhu, Hong-Yu Gao, Jin-Lan Xie, Feng-Ling Liao, Enrico Pira, Wei Zheng. Effective treatment of manganese-induced occupational Parkinsonism with p-aminosalicylic acid: a case of 17-year follow-up study. Journal of Occupational and Environmental Medicine. 2006-06, 48 (6): 644–649 [2019-02-12]. ISSN 1076-2752. PMC 4180660 . PMID 16766929. doi:10.1097/01.jom.0000204114.01893.3e. （原始内容存档于2019-05-21）.
^ Das, K. M.; Eastwood, M. A.; McManus, J. P. A.; Sircus, W. Adverse Reactions during Salicylazosulfapyridine Therapy and the Relation with Drug Metabolism and Acetylator Phenotype. New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS)). 1973-09-06, 289 (10): 491–495. ISSN 0028-4793. doi:10.1056/nejm197309062891001.
^ A. Szeinberg, C. Sheba, N. Hirshorn, E. Bodonyi. Studies on erthrocytes in cases with past history of favism and drug-induced acute hemolytic anemia. Blood. 1957-07, 12 (7): 603–613 [2019-02-12]. ISSN 0006-4971. PMID 13436516. （原始内容存档于2019-05-22）.
^ A. G. Macgregor, A. R. Somner. The anti-thyroid action of para-aminosalicylic acid. Lancet (London, England). 1954-11-06, 267 (6845): 931–936 [2019-02-12]. ISSN 0140-6736. PMID 13213079. （原始内容存档于2019-05-22）.
^ Boman G. Serum concentration and half-life of rifampicin after simultaneous oral administration of aminosalicylic acid or isoniazid. European journal of clinical pharmacology. 1974, 7 (3): 217–25. PMID 4854257. doi:10.1007/BF00560384.
^ J. Lehmann. Para-aminosalicylic acid in the treatment of tuberculosis. Lancet (London, England). 1946-01-05, 1 (6384): 15 [2019-02-12]. ISSN 0140-6736. PMID 21008766. （原始内容存档于2019-05-19）.
^ Mitchell, Stephen C.; Waring, Rosemary H., Aminophenols, Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2000-09-15, ISBN 3-527-30673-0, doi:10.1002/14356007.a02_099

[long-1] 1.0 ^1.1 ^1.2 W. Fox, G. A. Ellard, D. A. Mitchison. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. The International Journal of Tuberculosis and Lung Disease: The Official Journal of the International Union Against Tuberculosis and Lung Disease. 1999-10, 3 (10 Suppl 2): S231–279 [2019-02-12]. ISSN 1027-3719. PMID 10529902. （原始内容存档于2019-05-22）.

[xl-2] 2.0 ^2.1 Daniel F, Seksik P, Cacheux W, Jian R, Marteau P. Tolerance of 4-aminosalicylic acid enemas in patients with inflammatory bowel disease and 5-aminosalicylic-induced acute pancreatitis. Inflamm Bowel Dis. 2004, 10 (3): 258–260. PMID 15290921. doi:10.1097/00054725-200405000-00013.

[3] C. Vetuschi, G. Ragno, P. Mazzeo. Determination of p-aminosalicylic acid and m-aminophenol by derivative UV-spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis. 1988, 6 (4): 383–391 [2019-02-12]. ISSN 0731-7085. PMID 16867404. （原始内容存档于2019-05-22）.

[4] Mitchison DA. Role of individual drugs in the chemotherapy of tuberculosis Role of individual drugs in the chemotherapy of tuberculosis. Int J Tuberc Lung Dis. 2000, 4 (9): 796–806. PMID 10985648.

[5] Paser. RxList. [2008-10-10]. （原始内容存档于2008-10-25）.

[6] Smith NP, Ryan TJ, Sanderson KV, Sarkany I. Lichen scrofulosorum: A report of four cases. Br J Dermatol. 1976, 94 (3): 319–325. PMID 1252363. doi:10.1111/j.1365-2133.1976.tb04391.x.

[7] Black JM; Sutherland, IB. Two incidents of tuberculous infection by milk from attested herds. Br Med J. 1961, 1 (5241): 1732–1735. PMC 1954350 . PMID 20789163. doi:10.1136/bmj.1.5241.1732.

[8] Yue-Ming Jiang, Xue-An Mo, Feng-Qi Du, Xue Fu, Xia-Yan Zhu, Hong-Yu Gao, Jin-Lan Xie, Feng-Ling Liao, Enrico Pira, Wei Zheng. Effective treatment of manganese-induced occupational Parkinsonism with p-aminosalicylic acid: a case of 17-year follow-up study. Journal of Occupational and Environmental Medicine. 2006-06, 48 (6): 644–649 [2019-02-12]. ISSN 1076-2752. PMC 4180660 . PMID 16766929. doi:10.1097/01.jom.0000204114.01893.3e. （原始内容存档于2019-05-21）.

[9] Das, K. M.; Eastwood, M. A.; McManus, J. P. A.; Sircus, W. Adverse Reactions during Salicylazosulfapyridine Therapy and the Relation with Drug Metabolism and Acetylator Phenotype. New England Journal of Medicine (New England Journal of Medicine (NEJM/MMS)). 1973-09-06, 289 (10): 491–495. ISSN 0028-4793. doi:10.1056/nejm197309062891001.

[10] A. Szeinberg, C. Sheba, N. Hirshorn, E. Bodonyi. Studies on erthrocytes in cases with past history of favism and drug-induced acute hemolytic anemia. Blood. 1957-07, 12 (7): 603–613 [2019-02-12]. ISSN 0006-4971. PMID 13436516. （原始内容存档于2019-05-22）.

[11] A. G. Macgregor, A. R. Somner. The anti-thyroid action of para-aminosalicylic acid. Lancet (London, England). 1954-11-06, 267 (6845): 931–936 [2019-02-12]. ISSN 0140-6736. PMID 13213079. （原始内容存档于2019-05-22）.

[12] Boman G. Serum concentration and half-life of rifampicin after simultaneous oral administration of aminosalicylic acid or isoniazid. European journal of clinical pharmacology. 1974, 7 (3): 217–25. PMID 4854257. doi:10.1007/BF00560384.

[13] J. Lehmann. Para-aminosalicylic acid in the treatment of tuberculosis. Lancet (London, England). 1946-01-05, 1 (6384): 15 [2019-02-12]. ISSN 0140-6736. PMID 21008766. （原始内容存档于2019-05-19）.

[Mitchell_Waring-14] Mitchell, Stephen C.; Waring, Rosemary H., Aminophenols, Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2000-09-15, ISBN 3-527-30673-0, doi:10.1002/14356007.a02_099

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