使用者:ThomasYehYeh/沙盒/伊朗罪案

**ThomasYehYeh/沙盒/伊朗罪案**
	[[File:artemether.svg yiy\|150px]]
臨床資料
商品名（英語：Drug nomenclature）	許多
AHFS/Drugs.com	國際藥品名稱
給藥途徑	肌肉注射，口服給藥
ATC碼	P01BE02 (WHO) ;
法律規範狀態
法律規範	英：處方藥（℞-only） (POM); 處方藥（℞-only）;
識別資訊
	IUPAC命名法 (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-methoxy-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]-2-benzopyran; ;
CAS號	71963-77-4
PubChem CID	68911;
DrugBank	DB06697 ;
ChemSpider	62138 ;
UNII	C7D6T3H22J;
KEGG	D02483 ;
ChEBI	CHEBI:195280 ;
PDB配體ID	D8Z (PDBe, RCSB PDB);
化學資訊
化學式	C16H26O5
摩爾質量	298.38 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
熔點	86至88 °C（187至190 °F）
	SMILES C[C@@H]1CC[C@@H]3C42OO[C@](C)(CC[C@@H]12)O[C@H]4O[C@H](OC)[C@@H]3C;
	InChI InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13+,14-,15-,16-/m1/s1 ; Key:SXYIRMFQILZOAM-HVNFFKDJSA-N ;

蒿甲醚（英語：artemethe）是一種用於治療瘧疾的藥物。^[1]^[2]遇到嚴重的瘧疾，會採專用的肌肉注射劑進行治療，而非使用奎寧。^[2]此藥物對於成人患者的效果可能不如青蒿琥酯顯著。^[2]除肌肉注射劑外，^[2]也有與苯芴醇合併成為複方形式的口服劑（蒿甲醚/苯芴醇）。^[1]^[3]

使用蒿甲醚產生的副作用相對較少，^[4]可能會發生心律不整，但屬於罕見。^[4]雖然有證據顯示動物於懷孕期間使用可能對其胎兒有害，但尚無證據顯示對人類有影響。^[4]因此世界衛生組織 (WHO) 建議個體在懷孕期間可使用。^[4]此藥物是青蒿素類藥物中的一種。^[4]

醫界至少從1981年就開始研究蒿甲醚，此藥物於1987年被核准用作醫療用途。^[5]它已被納入世界衛生組織基本藥物標準清單之中。^[6]

醫療用途

蒿甲醚是一種抗瘧疾藥物，用於治療惡性瘧原蟲（和抗氯化奎寧惡性瘧原蟲）或抗氯化奎寧間日瘧原蟲引起的單純性瘧疾。^[1]^[7]蒿甲醚也可用於治療嚴重性瘧疾。^[2]

WHO建議使用以青蒿素為主的聯合療法治療無併發症的惡性瘧原蟲感染。^[8]與苯芴醇合併使用後，可進行為期14天的普來馬奎寧治療方案，以預防間日瘧原蟲或卵形瘧原蟲感染復發，以徹底治癒。^[9]

蒿甲醚與吡喹酮（驅蟲藥）聯合也可用於治療及預防血吸蟲病原蟲感染。^[10]

美國食品藥物管理局（FDA）根據在動物身上的研究結果，將青蒿素衍生物歸為C類，表示青蒿素衍生物與胎兒流產和致畸有關聯。然而另有一些研究並未發現有害的證據。^[11]^[12]

使用蒿甲醚/苯芴醇的個體進行母乳哺育可能對於嬰兒並不安全，在使用前應進行醫療諮詢。^[13]本藥物不適合兩個月以下，或是體重不足11磅（約5公斤）的嬰兒使用。^[13]

副作用

使用蒿甲醚可能產生的副作用有心臟方面的問題，例如心跳過緩和心電圖QT間期延長（QT間期過長或過短可能代表心律不整和心臟驟停的風險較高）。^[1]^[14]此外，在動物的研究已顯示可能會產生中樞神經系統毒性。^[15]^[16]

禁忌症

個體於第一個孕期（第1到第13週）使用此藥物可能會傷害胎兒，不宜使用。^[17]

藥物會導致輕度至中毒肝損傷，但無須調整劑量。有嚴重肝損傷的個體使用時則需謹慎。^[17]

藥物交互作用

當蒿甲醚與抗愛滋病藥物洛匹那韋/利托那韋一起使用時，會導致血漿中的蒿甲醚水平較低。^[16]與依法韋侖（治療和預防愛滋病藥物）或奈韋拉平（預防愛滋病藥物）同時使用也會降低蒿甲醚於血漿中的濃度。^[18]^[19]

蒿甲醚/苯芴醇複方劑不應與抑制細胞色素CYP3A4的藥物一起使用。^[1]^[20]

激素避孕藥與蒿甲醚/苯芴醇一起使用時，避孕效果會被降低。^[20]

藥理學

作用機轉

青蒿素類藥物的作用機轉可能是透過抑制鈣離子三磷酸腺苷酶（英語：PfATP6）（PfATP6）而發揮原蟲殺傷作用。由於PfATP6是一種調節細胞鈣濃度的酶，其功能失調會導致細胞內鈣積累，最終細胞因而死亡。^[21]

藥物動力學

使用此藥物，而同時進行飲食，可將藥物的吸收率提高2至3倍。它會與蛋白質高度結合（95.4%）。給藥2小時後出現蒿甲醚的最大血藥濃度。^[3]

蒿甲醚在人體內主要經由肝臟酵素CYP3A4/CYP3A5（英語：CYP3A5）代謝為活性代謝產物 - 二氫青蒿素。^[3]蒿甲醚母體藥物和活性代謝物的生物半衰期約為2小時。^[3]

化學

蒿甲醚是青蒿素的甲醚衍生物，青蒿素是從抗瘧疾植物黃花蒿中分離出的一種含過氧化物的內酯。它也被稱為二氫青蒿素甲醚，其國際化聯名稱為(+)-(3-α,5a-β,6-β,8a-β,9-α,12-β,12aR )-decaHydro-10 -甲氧基-3,6,9-三甲基-3,12-環氧-12H-吡喃(4,3-j)-1,2-苯並二氧雜環己烷。此藥物是一種相對親脂性和不穩定的藥物，^[22]此藥物除會影響瘧原蟲的膜運輸系統外，也會產生反應性自由基以攻擊瘧原蟲的細胞結構而發揮作用。^[14]

歷史

青蒿素是一種極佳的瘧疾治療藥物。然而多年來的供應一直不穩定。該藥物的唯一來源是生長在東南亞的黃花蒿，但生產循著一種惡性循環模式進行。農民僅在價格高時才願意種植，不可避免的會供過於求而導致價格下跌，之後產量下降，再次將價格推高。總部位於法國巴黎的賽諾菲製藥曾於2013年推出合成法製造，但生產成本不敵種植黃花蒿生產的。目前製藥界正致力，試圖由黃花蒿中萃取更多的青蒿素及其衍生物。^[23]

參考文獻

^ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 Artemether and Lumefantrine (Monograph). Drugs.com. 2023-02-22 [2024-02-17].
^ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 Esu EB, Effa EE, Opie ON, Meremikwu MM. Artemether for severe malaria. The Cochrane Database of Systematic Reviews. June 2019, 6 (6): CD010678. PMC 6580442 . PMID 31210357. doi:10.1002/14651858.CD010678.pub3.
^ ^3.0 ^3.1 ^3.2 ^3.3 Coartem- artemether and lumefantrine tablet. DailyMed. 2019-08-05 [2020-04-26].
^ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 Kovacs SD, Rijken MJ, Stergachis A. Treating severe malaria in pregnancy: a review of the evidence. Drug Safety. February 2015, 38 (2): 165–181. PMC 4328128 . PMID 25556421. doi:10.1007/s40264-014-0261-9.
^ Rao Y, Zhang D, Li R. Tu Youyou and the Discovery of Artemisinin: 2015 Nobel Laureate in Physiology or Medicine. World Scientific. 2016: 162. ISBN 9789813109919. （原始內容存檔於2017-09-10）.
^ 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.
^ Makanga M, Krudsood S. The clinical efficacy of artemether/lumefantrine (Coartem). Malaria Journal. October 2009, 8 (Suppl 1): S5. PMC 2760240 . PMID 19818172. doi:10.1186/1475-2875-8-S1-S5 .
^ Treatment of Uncomplicated Plasmodium falciparum Malaria. World Health Organization. 2015-01-01. （原始內容存檔於2017-09-10）.
^ Treatment Of Uncomplicated Malaria Caused By P. vivax, P. ovale, P. malariae or P. knowlesi. World Health Organization. 2015-01-01. （原始內容存檔於2017-09-10）.
^ Pérez del Villar L, Burguillo FJ, López-Abán J, Muro A. Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis. PLOS ONE. 2012-01-01, 7 (9): e45867. Bibcode:2012PLoSO...745867P. PMC 3448694 . PMID 23029285. doi:10.1371/journal.pone.0045867 .
^ Dellicour S, Hall S, Chandramohan D, Greenwood B. The safety of artemisinins during pregnancy: a pressing question. Malaria Journal. February 2007, 6: 15. PMC 1802871 . PMID 17300719. doi:10.1186/1475-2875-6-15 .
^ Piola P, Nabasumba C, Turyakira E, Dhorda M, Lindegardh N, Nyehangane D, et al. Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. The Lancet. Infectious Diseases. November 2010, 10 (11): 762–769. PMID 20932805. doi:10.1016/S1473-3099(10)70202-4. hdl:10144/116337 .
^ ^13.0 ^13.1 Artemether and lumefantrine. Drugs.com. [2024-08-17].
^ ^14.0 ^14.1 Artemether. www.antimicrobe.org. [2016-11-09]. （原始內容存檔於2017-02-23）.
^ WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition: Protozoa: Malaria: Artemether. apps.who.int. [2016-11-09]. （原始內容存檔於2016-11-10）.
^ ^16.0 ^16.1 Askling HH, Bruneel F, Burchard G, Castelli F, Chiodini PL, Grobusch MP, et al. Management of imported malaria in Europe. Malaria Journal. September 2012, 11: 328. PMC 3489857 . PMID 22985344. doi:10.1186/1475-2875-11-328 .
^ ^17.0 ^17.1 Artemether. Pediatric Oncall. [2024-08-17].
^ Van Geertruyden JP. Interactions between malaria and human immunodeficiency virus anno 2014. Clinical Microbiology and Infection. April 2014, 20 (4): 278–285. PMC 4368411 . PMID 24528518. doi:10.1111/1469-0691.12597.
^ Kiang TK, Wilby KJ, Ensom MH. Clinical pharmacokinetic drug interactions associated with artemisinin derivatives and HIV-antivirals. Clinical Pharmacokinetics. February 2014, 53 (2): 141–153. PMID 24158666. S2CID 1281113. doi:10.1007/s40262-013-0110-5.
^ ^20.0 ^20.1 Stover KR, King ST, Robinson J. Artemether-lumefantrine: an option for malaria. The Annals of Pharmacotherapy. April 2012, 46 (4): 567–577. PMID 22496476. S2CID 7678606. doi:10.1345/aph.1Q539.
^ Guo Z. Artemisinin anti-malarial drugs in China. Acta Pharmaceutica Sinica. B. March 2016, 6 (2): 115–124. PMC 4788711 . PMID 27006895. doi:10.1016/j.apsb.2016.01.008.
^ De Spiegeleer BM, D'Hondt M, Vangheluwe E, Vandercruyssen K, De Spiegeleer BV, Jansen H, et al. Relative response factor determination of β-artemether degradants by a dry heat stress approach. Journal of Pharmaceutical and Biomedical Analysis. November 2012, 70: 111–116. PMID 22770733. doi:10.1016/j.jpba.2012.06.002. hdl:1854/LU-2938963 .
^ Molecule of the Week Archive Artemether. ACS. 2018-07-30 [2024-08-17].

[drugs-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 Artemether and Lumefantrine (Monograph). Drugs.com. 2023-02-22 [2024-02-17].

[Esu2019-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 Esu EB, Effa EE, Opie ON, Meremikwu MM. Artemether for severe malaria. The Cochrane Database of Systematic Reviews. June 2019, 6 (6): CD010678. PMC 6580442 . PMID 31210357. doi:10.1002/14651858.CD010678.pub3.

[Coartem_FDA_label-3] 3.0 ^3.1 ^3.2 ^3.3 Coartem- artemether and lumefantrine tablet. DailyMed. 2019-08-05 [2020-04-26].

[Kov2015-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 Kovacs SD, Rijken MJ, Stergachis A. Treating severe malaria in pregnancy: a review of the evidence. Drug Safety. February 2015, 38 (2): 165–181. PMC 4328128 . PMID 25556421. doi:10.1007/s40264-014-0261-9.

[5] Rao Y, Zhang D, Li R. Tu Youyou and the Discovery of Artemisinin: 2015 Nobel Laureate in Physiology or Medicine. World Scientific. 2016: 162. ISBN 9789813109919. （原始內容存檔於2017-09-10）.

[WHO21st-6] 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] Makanga M, Krudsood S. The clinical efficacy of artemether/lumefantrine (Coartem). Malaria Journal. October 2009, 8 (Suppl 1): S5. PMC 2760240 . PMID 19818172. doi:10.1186/1475-2875-8-S1-S5 .

[8] Treatment of Uncomplicated Plasmodium falciparum Malaria. World Health Organization. 2015-01-01. （原始內容存檔於2017-09-10）.

[9] Treatment Of Uncomplicated Malaria Caused By P. vivax, P. ovale, P. malariae or P. knowlesi. World Health Organization. 2015-01-01. （原始內容存檔於2017-09-10）.

[10] Pérez del Villar L, Burguillo FJ, López-Abán J, Muro A. Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis. PLOS ONE. 2012-01-01, 7 (9): e45867. Bibcode:2012PLoSO...745867P. PMC 3448694 . PMID 23029285. doi:10.1371/journal.pone.0045867 .

[11] Dellicour S, Hall S, Chandramohan D, Greenwood B. The safety of artemisinins during pregnancy: a pressing question. Malaria Journal. February 2007, 6: 15. PMC 1802871 . PMID 17300719. doi:10.1186/1475-2875-6-15 .

[12] Piola P, Nabasumba C, Turyakira E, Dhorda M, Lindegardh N, Nyehangane D, et al. Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. The Lancet. Infectious Diseases. November 2010, 10 (11): 762–769. PMID 20932805. doi:10.1016/S1473-3099(10)70202-4. hdl:10144/116337 .

[Drugs.com-13] 13.0 ^13.1 Artemether and lumefantrine. Drugs.com. [2024-08-17].

[Artemether-14] 14.0 ^14.1 Artemether. www.antimicrobe.org. [2016-11-09]. （原始內容存檔於2017-02-23）.

[15] WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition: Protozoa: Malaria: Artemether. apps.who.int. [2016-11-09]. （原始內容存檔於2016-11-10）.

[Askling2012-16] 16.0 ^16.1 Askling HH, Bruneel F, Burchard G, Castelli F, Chiodini PL, Grobusch MP, et al. Management of imported malaria in Europe. Malaria Journal. September 2012, 11: 328. PMC 3489857 . PMID 22985344. doi:10.1186/1475-2875-11-328 .

[Pediatric_Oncall-17] 17.0 ^17.1 Artemether. Pediatric Oncall. [2024-08-17].

[18] Van Geertruyden JP. Interactions between malaria and human immunodeficiency virus anno 2014. Clinical Microbiology and Infection. April 2014, 20 (4): 278–285. PMC 4368411 . PMID 24528518. doi:10.1111/1469-0691.12597.

[19] Kiang TK, Wilby KJ, Ensom MH. Clinical pharmacokinetic drug interactions associated with artemisinin derivatives and HIV-antivirals. Clinical Pharmacokinetics. February 2014, 53 (2): 141–153. PMID 24158666. S2CID 1281113. doi:10.1007/s40262-013-0110-5.

[Stover2012-20] 20.0 ^20.1 Stover KR, King ST, Robinson J. Artemether-lumefantrine: an option for malaria. The Annals of Pharmacotherapy. April 2012, 46 (4): 567–577. PMID 22496476. S2CID 7678606. doi:10.1345/aph.1Q539.

[Guo2016-21] Guo Z. Artemisinin anti-malarial drugs in China. Acta Pharmaceutica Sinica. B. March 2016, 6 (2): 115–124. PMC 4788711 . PMID 27006895. doi:10.1016/j.apsb.2016.01.008.

[22] De Spiegeleer BM, D'Hondt M, Vangheluwe E, Vandercruyssen K, De Spiegeleer BV, Jansen H, et al. Relative response factor determination of β-artemether degradants by a dry heat stress approach. Journal of Pharmaceutical and Biomedical Analysis. November 2012, 70: 111–116. PMID 22770733. doi:10.1016/j.jpba.2012.06.002. hdl:1854/LU-2938963 .

[23] Molecule of the Week Archive Artemether. ACS. 2018-07-30 [2024-08-17].

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