去鐵胺

去鐵胺
	Skeletal formula and spacefill model of deferoxamine
臨床資料
商品名（英語：Drug nomenclature）	Desferal
其他名稱	desferrioxamine B、desferoxamine B、DFO-B, DFB及N'-[5-(Acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino]pentyl]-N-hydroxy-butane diamide
AHFS/Drugs.com	Monograph
給藥途徑	肌肉注射; 靜脈注射; 皮下注射;
ATC碼	V03AC01 (WHO) ;
藥物動力學數據
生物半衰期	6小時
識別資訊
	IUPAC命名法 N'5-[Acetyl(hydroxy)amino]pentylN-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-N-hydroxysuccinamide; ;
CAS編號	70-51-9（）
PubChem CID	2973;
DrugBank	DB00746;
ChemSpider	2867;
UNII	J06Y7MXW4D;
KEGG	D03670;
ChEBI	CHEBI:4356;
ChEMBL	ChEMBL556;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID7022887 ;
ECHA InfoCard	100.000.671
化學資訊
化學式	C25H48N6O8
莫耳質量	560.69 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN;
	InChI InChI=1S/C25H48N6O8/c1-21(32)29(37)18-9-3-6-16-27-22(33)12-14-25(36)31(39)20-10-4-7-17-28-23(34)11-13-24(35)30(38)19-8-2-5-15-26/h37-39H,2-20,26H2,1H3,(H,27,33)(H,28,34); ; Key:UBQYURCVBFRUQT-UHFFFAOYSA-N;

去鐵胺 （英語：Deferoxamine ，簡稱DFOA，也可寫為desferrioxamine），以Desferal品牌在市面銷售，是一種可與鐵和鋁結合的藥物，^[1]專門用於治療鐵中毒、因多次輸血或具有遺傳性疾病而導致的血色沉著病以及個體因透析導致鋁中毒（英語：Aluminium toxicity in people on dialysis）。^[1]^[2]此藥物係透過肌肉注射、靜脈注射或皮下注射方式給藥。^[1]

Quick Facts 臨床資料, 商品名（英語：Drug nomenclature） ...

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使用後常見的副作用有注射部位疼痛、腹瀉、嘔吐、發燒、聽力損失和眼睛問題。^[1]可能會發生嚴重過敏反應，包括過敏性休克和低血壓。^[1]目前尚不清楚個體於懷孕期間使用是否會對胎兒，或是哺乳期間使用是否會對嬰兒產生安全上的問題。^[3]此藥物是由革蘭氏陽性菌毛鏈黴菌（英語：Streptomyces pilosus）提煉出的的螯鐵素（英語：siderophore）製成。^[4]^[5]

去鐵胺於1968年在美國被批准用於醫療用途。^[1]它已被列入世界衛生組織基本藥物標準清單之中。^[6]

去鐵胺用於治療急性鐵中毒（尤其是幼兒的^[7]）。此藥物也常用於治療血色沉著病（一種遺傳性或後天性體內鐵累積疾病）。後天性血色沉著常見於患有某些慢性貧血（例如地中海貧血和骨髓增生異常症候群）的患者，由於他們需要多次輸血，而會大幅增加體內的鐵含量。使用鐵螯合藥物（例如去鐵胺）治療，可降低依賴輸血維生的鐮刀型紅血球疾病或β型地中海貧血（英語：Beta thalassemias）患者的死亡率。^[8]

針對慢性病症，通常透過每天間隔8-12小時的皮下注射給藥。急性中毒後使用去鐵胺可能會導致尿液呈現粉紅色，此現象稱為"桃紅葡萄酒尿液（法語：vin rosé urine）"。除用於治療鐵中毒之外，還可用於治療特定患者的鋁中毒（體內鋁過量）（但尚未獲得美國食品藥物管理局（FDA）批准用於此用途）。去鐵胺也用於將阿黴素的心臟毒性副作用作最大限度降低，以及治療鐵藍蛋白缺乏症（英語：aceruloplasminemia）。^[9]去鐵胺可能有效改善顱內出血患者的神經系統，但支持此適應症的有效性和安全性的證據很弱。^[10]

一些發表的文章提出COVID-19確診者的體內鐵蛋白水平較高，而建議施用此藥物。^[11]^[12]

目前尚不清楚個體於懷孕期間使用是否會對胎兒產生安全上的問題。^[3]

罹患地中海貧血患者中屬於thalassemia major類型的，長期使用此藥物可能會增加其聽力損失的風險。^[13]

長期使用去鐵胺可能會引起眼睛症狀、生長遲緩（英語：Delayed milestone）、局部反應和過敏。^[14]

去鐵胺是是由革蘭氏陽性菌毛鏈黴菌所產生的螯鐵素B，將其中三價鐵離子部分移除而製成。發現此藥物是汽巴精化（精細化工生產商）與瑞士蘇黎世聯邦理工學院和德國弗萊堡大學醫院（英語：University Medical Center Freiburg）的科學家合作研究中無意中發現的結果。^[15]^[4]去鐵胺通過結合血液中的遊離鐵，也增強經由尿液消除。此藥物可去除血色沉著症患者體內多餘的鐵，而減少對各種器官和組織（例如肝臟）造成損害。此外目前有有限的證據支持其能加速神經損傷的癒合。^[16]去鐵胺可調節特定細胞類型^[17]發炎介質的表達^[18]和釋放。

目前有研究使用去鐵胺於治療脊髓損傷^[19]和顱內出血。^[20]^[21]它也用於研究誘導間充質幹細胞中發生缺氧樣環境（可激活一些與缺氧相關的信號通路，這些通路通常在缺氧環境下受激活後會發揮各種細胞保護作用）。^[22]^[23]

由於去鐵胺的末端胺基不會與金屬螯合，因此被用於固定到各種工業和生物醫學應用的表面和基材上（例如固定在過濾器上，用於去除水中的鐵離子，固定在生物傳感器的表面上，用於檢測體液中的鐵離子含量）。^[24]

螯合療法（英語：Chelation therapy）
解鐵定

[1]
Deferoxamine Mesylate. The American Society of Health-System Pharmacists. [2016-12-08]. （原始內容存檔於2016-12-21）.
[2]
World Health Organization. Stuart MC, Kouimtzi M, Hill SR , 編. WHO Model Formulary 2008. World Health Organization. 2009: 61–62. ISBN 9789241547659. hdl:10665/44053 .
[3]
Deferoxamine (Desferal) Use During Pregnancy. www.drugs.com. [2016-12-13]. （原始內容存檔於2016-12-21）.
[4]
Giardina PJ, Rivella S. Thalassemia Syndromes. Hoffman R, Benz Jr EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J (編). Hematology: Diagnosis and Treatment 6th. Elsevier Health Sciences. 2012: 515. ISBN 978-1-4557-4041-3. （原始內容存檔於2016-12-20）（英語）.
[5]
Keberle H. The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism. Annals of the New York Academy of Sciences. October 1964, 119 (2): 758–768. PMID 14219455. S2CID 37277528. doi:10.1111/j.1749-6632.1965.tb54077.x.
[6]
World Health Organization. World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. hdl:10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
[7]
Merlot AM, Kalinowski DS, Richardson DR. Novel chelators for cancer treatment: where are we now?. Antioxidants & Redox Signaling. March 2013, 18 (8): 973–1006. PMID 22424293. doi:10.1089/ars.2012.4540.
[8]
Ballas SK, Zeidan AM, Duong VH, DeVeaux M, Heeney MM. The effect of iron chelation therapy on overall survival in sickle cell disease and β-thalassemia: A systematic review. American Journal of Hematology. July 2018, 93 (7): 943–952. PMID 29635754. doi:10.1002/ajh.25103 .
[9]
Miyajima H, Takahashi Y, Kamata T, Shimizu H, Sakai N, Gitlin JD. Use of desferrioxamine in the treatment of aceruloplasminemia. Annals of Neurology. March 1997, 41 (3): 404–407. PMID 9066364. S2CID 22425032. doi:10.1002/ana.410410318.
[10]
Zeng L, Tan L, Li H, Zhang Q, Li Y, Guo J. Deferoxamine therapy for intracerebral hemorrhage: A systematic review. PLOS ONE. 2018, 13 (3): e0193615. Bibcode:2018PLoSO..1393615Z. PMC 5863956 . PMID 29566000. doi:10.1371/journal.pone.0193615 .
[11]
Abobaker A. Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome?. European Journal of Clinical Pharmacology. November 2020, 76 (11): 1619–1620. PMC 7325475 . PMID 32607779. doi:10.1007/s00228-020-02942-9.
[12]
Alkattan A, Alabdulkareem K, Kamel A, Abdelseed H, Almutairi Y, Alsalameen E. Correlation between Micronutrient plasma concentration and disease severity in COVID-19 patients.. Alexandria Journal of Medicine. January 2021, 57 (1): 21–27. PMC 8108185 . doi:10.1080/20905068.2020.1870788.
[13]
Badfar G, Mansouri A, Shohani M, Karimi H, Khalighi Z, Rahmati S, et al. Hearing loss in Iranian thalassemia major patients treated with deferoxamine: A systematic review and meta-analysis. Caspian Journal of Internal Medicine. 2017, 8 (4): 239–249. PMC 5686301 . PMID 29201313. doi:10.22088/cjim.8.4.239.
[14]
Taher AT, Musallam KM, Cappellini MD. β-Thalassemias. The New England Journal of Medicine. February 2021, 384 (8): 727–743. PMID 33626255. S2CID 232049825. doi:10.1056/NEJMra2021838.
[15]
Yawalkar SJ. Milestones in the research and development of desferrioxamine. Nephrology, Dialysis, Transplantation. 1993, 8 (Suppl 1): 40–42. PMID 8389019. doi:10.1093/ndt/8.supp1.40.
[16]
Xu, Weilin; Guo, Zhen-Ni. Editorial: Ferroptosis in stroke, neurotrauma and neurodegeneration, volume II. Frontiers in Cellular Neuroscience. 2023-07-05 [2023-4-04-26]. doi:10.3389/fncel.2023.1238425. （原始內容存檔於2024-04-26）.
[17]
Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, et al. Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways. Journal of Immunology. June 2004, 172 (11): 7069–7077. PMID 15153529. doi:10.4049/jimmunol.172.11.7069 .
[18]
Lee HJ, Lee J, Lee SK, Lee SK, Kim EC. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. BMC Cancer. September 2007, 7: 176. PMC 2078595 . PMID 17850672. doi:10.1186/1471-2407-7-176 .
[19]
Public summary of opinion on orphan designation: Deferoxamine mesylate for the treatment of traumatic spinal cord injury. Committee for Orphan Medicinal Products. European Medicines Agency. 2013-10-03. （原始內容存檔於2013-07-17）.
[20]
Wu H, Wu T, Xu X, Wang J, Wang J. Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. Journal of Cerebral Blood Flow and Metabolism. May 2011, 31 (5): 1243–1250. PMC 3099628 . PMID 21102602. doi:10.1038/jcbfm.2010.209.
[21]
Ren H, Han R, Chen X, Liu X, Wan J, Wang L, et al. Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update. Journal of Cerebral Blood Flow and Metabolism. September 2020, 40 (9): 1752–1768. PMC 7446569 . PMID 32423330. doi:10.1177/0271678X20923551.
[22]
Ren H, Cao Y, Zhao Q, Li J, Zhou C, Liao L, et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochemical and Biophysical Research Communications. August 2006, 347 (1): 12–21. PMID 16814746. doi:10.1016/j.bbrc.2006.05.169.
[23]
Woo KJ, Lee TJ, Park JW, Kwon TK. Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway. Biochemical and Biophysical Research Communications. April 2006, 343 (1): 8–14. PMID 16527254. doi:10.1016/j.bbrc.2006.02.116.
[24]
Touma, J. G.; Kelly, C.; Coblyn, M.; Jovanovic, G. N.; Schilke, K. Reversible Covalent Binding of Desferrioxamine B (DFOB) to Polystyrene Microspheres for the Chelation of Aqueous Iron Citrate. Industrial & Engineering Chemistry Research. 2023, 62 (37): 15109–15119. doi:10.1021/acs.iecr.3c00812.

[AHFS2016-1] [1]
Deferoxamine Mesylate. The American Society of Health-System Pharmacists. [2016-12-08]. （原始內容存檔於2016-12-21）.

[WHO2008-2] [2]
World Health Organization. Stuart MC, Kouimtzi M, Hill SR , 編. WHO Model Formulary 2008. World Health Organization. 2009: 61–62. ISBN 9789241547659. hdl:10665/44053 .

[drugs.com-3] [3]
Deferoxamine (Desferal) Use During Pregnancy. www.drugs.com. [2016-12-13]. （原始內容存檔於2016-12-21）.

[Elsevier_Health_Sciences-4] [4]
Giardina PJ, Rivella S. Thalassemia Syndromes. Hoffman R, Benz Jr EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J (編). Hematology: Diagnosis and Treatment 6th. Elsevier Health Sciences. 2012: 515. ISBN 978-1-4557-4041-3. （原始內容存檔於2016-12-20）（英語）.

[5] [5]
Keberle H. The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism. Annals of the New York Academy of Sciences. October 1964, 119 (2): 758–768. PMID 14219455. S2CID 37277528. doi:10.1111/j.1749-6632.1965.tb54077.x.

[WHO21st-6] [6]
World Health Organization. World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. hdl:10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.

[7] [7]
Merlot AM, Kalinowski DS, Richardson DR. Novel chelators for cancer treatment: where are we now?. Antioxidants & Redox Signaling. March 2013, 18 (8): 973–1006. PMID 22424293. doi:10.1089/ars.2012.4540.

[8] [8]
Ballas SK, Zeidan AM, Duong VH, DeVeaux M, Heeney MM. The effect of iron chelation therapy on overall survival in sickle cell disease and β-thalassemia: A systematic review. American Journal of Hematology. July 2018, 93 (7): 943–952. PMID 29635754. doi:10.1002/ajh.25103 .

[acerulo1-9] [9]
Miyajima H, Takahashi Y, Kamata T, Shimizu H, Sakai N, Gitlin JD. Use of desferrioxamine in the treatment of aceruloplasminemia. Annals of Neurology. March 1997, 41 (3): 404–407. PMID 9066364. S2CID 22425032. doi:10.1002/ana.410410318.

[10] [10]
Zeng L, Tan L, Li H, Zhang Q, Li Y, Guo J. Deferoxamine therapy for intracerebral hemorrhage: A systematic review. PLOS ONE. 2018, 13 (3): e0193615. Bibcode:2018PLoSO..1393615Z. PMC 5863956 . PMID 29566000. doi:10.1371/journal.pone.0193615 .

[pmid32607779-11] [11]
Abobaker A. Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome?. European Journal of Clinical Pharmacology. November 2020, 76 (11): 1619–1620. PMC 7325475 . PMID 32607779. doi:10.1007/s00228-020-02942-9.

[12] [12]
Alkattan A, Alabdulkareem K, Kamel A, Abdelseed H, Almutairi Y, Alsalameen E. Correlation between Micronutrient plasma concentration and disease severity in COVID-19 patients.. Alexandria Journal of Medicine. January 2021, 57 (1): 21–27. PMC 8108185 . doi:10.1080/20905068.2020.1870788.

[13] [13]
Badfar G, Mansouri A, Shohani M, Karimi H, Khalighi Z, Rahmati S, et al. Hearing loss in Iranian thalassemia major patients treated with deferoxamine: A systematic review and meta-analysis. Caspian Journal of Internal Medicine. 2017, 8 (4): 239–249. PMC 5686301 . PMID 29201313. doi:10.22088/cjim.8.4.239.

[Taher-14] [14]
Taher AT, Musallam KM, Cappellini MD. β-Thalassemias. The New England Journal of Medicine. February 2021, 384 (8): 727–743. PMID 33626255. S2CID 232049825. doi:10.1056/NEJMra2021838.

[15] [15]
Yawalkar SJ. Milestones in the research and development of desferrioxamine. Nephrology, Dialysis, Transplantation. 1993, 8 (Suppl 1): 40–42. PMID 8389019. doi:10.1093/ndt/8.supp1.40.

[16] [16]
Xu, Weilin; Guo, Zhen-Ni. Editorial: Ferroptosis in stroke, neurotrauma and neurodegeneration, volume II. Frontiers in Cellular Neuroscience. 2023-07-05 [2023-4-04-26]. doi:10.3389/fncel.2023.1238425. （原始內容存檔於2024-04-26）.

[17] [17]
Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, et al. Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways. Journal of Immunology. June 2004, 172 (11): 7069–7077. PMID 15153529. doi:10.4049/jimmunol.172.11.7069 .

[18] [18]
Lee HJ, Lee J, Lee SK, Lee SK, Kim EC. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. BMC Cancer. September 2007, 7: 176. PMC 2078595 . PMID 17850672. doi:10.1186/1471-2407-7-176 .

[19] [19]
Public summary of opinion on orphan designation: Deferoxamine mesylate for the treatment of traumatic spinal cord injury. Committee for Orphan Medicinal Products. European Medicines Agency. 2013-10-03. （原始內容存檔於2013-07-17）.

[pmid21102602-20] [20]
Wu H, Wu T, Xu X, Wang J, Wang J. Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. Journal of Cerebral Blood Flow and Metabolism. May 2011, 31 (5): 1243–1250. PMC 3099628 . PMID 21102602. doi:10.1038/jcbfm.2010.209.

[pmid32423330-21] [21]
Ren H, Han R, Chen X, Liu X, Wan J, Wang L, et al. Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update. Journal of Cerebral Blood Flow and Metabolism. September 2020, 40 (9): 1752–1768. PMC 7446569 . PMID 32423330. doi:10.1177/0271678X20923551.

[22] [22]
Ren H, Cao Y, Zhao Q, Li J, Zhou C, Liao L, et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochemical and Biophysical Research Communications. August 2006, 347 (1): 12–21. PMID 16814746. doi:10.1016/j.bbrc.2006.05.169.

[23] [23]
Woo KJ, Lee TJ, Park JW, Kwon TK. Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway. Biochemical and Biophysical Research Communications. April 2006, 343 (1): 8–14. PMID 16527254. doi:10.1016/j.bbrc.2006.02.116.

[24] [24]
Touma, J. G.; Kelly, C.; Coblyn, M.; Jovanovic, G. N.; Schilke, K. Reversible Covalent Binding of Desferrioxamine B (DFOB) to Polystyrene Microspheres for the Chelation of Aqueous Iron Citrate. Industrial & Engineering Chemistry Research. 2023, 62 (37): 15109–15119. doi:10.1021/acs.iecr.3c00812.

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去鐵胺

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去鐵胺

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醫療用途

不良影響

作用機制

研究

參見

參考文獻