用户:ThomasYehYeh/沙盒/伊朗罪案

**ThomasYehYeh/沙盒/伊朗罪案**
	[[File:artemether.svg yiy\|150px]]
临床资料
商品名（英语：Drug nomenclature）	许多
AHFS/Drugs.com	国际药品名称
给药途径	肌肉注射，口服给药
ATC码	P01BE02 (WHO) ;
法律规范状态
法律规范	英：处方药（℞-only） (POM); 处方药（℞-only）;
识别信息
	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号	71963-77-4
PubChem CID	68911;
DrugBank	DB06697 ;
ChemSpider	62138 ;
UNII	C7D6T3H22J;
KEGG	D02483 ;
ChEBI	CHEBI:195280 ;
PDB配体ID	D8Z (PDBe, RCSB PDB);
化学信息
化学式	C16H26O5
摩尔质量	298.38 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
熔点	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（英语：artemethe）是一种用于治疗疟疾的药物。^[1]^[2]遇到严重的疟疾，会采专用的肌肉注射剂进行治疗，而非使用奎宁。^[2]此药物对于成人患者的效果可能不如青蒿琥酯显著。^[2]除肌肉注射剂外，^[2]也有与苯芴醇合并成为复方形式的口服剂（蒿甲醚/苯芴醇）。^[1]^[3]

使用蒿甲醚产生的副作用相对较少，^[4]可能会发生心律不整，但属于罕见。^[4]虽然有证据显示动物于怀孕期间使用可能对其胎儿有害，但尚无证据显示对人类有影响。^[4]因此世界卫生组织 (WHO) 建议个体在怀孕期间可使用。^[4]此药物是青蒿素类药物中的一种。^[4]

医界至少从1981年就开始研究蒿甲醚，此药物于1987年被核准用作医疗用途。^[5]它已被纳入世界卫生组织基本药物标准清单之中。^[6]

医疗用途

蒿甲醚是一种抗疟疾药物，用于治疗恶性疟原虫（和抗氯化奎宁恶性疟原虫）或抗氯化奎宁间日疟原虫引起的单纯性疟疾。^[1]^[7]蒿甲醚也可用于治疗严重性疟疾。^[2]

WHO建议使用以青蒿素为主的联合疗法治疗无并发症的恶性疟原虫感染。^[8]与苯芴醇合并使用后，可进行为期14天的普来马奎宁治疗方案，以预防间日疟原虫或卵形疟原虫感染复发，以彻底治愈。^[9]

蒿甲醚与吡喹酮（驱虫药）联合也可用于治疗及预防血吸虫病原虫感染。^[10]

美国食品药物管理局（FDA）根据在动物身上的研究结果，将青蒿素衍生物归为C类，表示青蒿素衍生物与胎儿流产和致畸有关联。然而另有一些研究并未发现有害的证据。^[11]^[12]

使用蒿甲醚/苯芴醇的个体进行母乳哺育可能对于婴儿并不安全，在使用前应进行医疗咨询。^[13]本药物不适合两个月以下，或是体重不足11磅（约5公斤）的婴儿使用。^[13]

副作用

使用蒿甲醚可能产生的副作用有心脏方面的问题，例如心跳过缓和心电图QT间期延长（QT间期过长或过短可能代表心律不整和心脏骤停的风险较高）。^[1]^[14]此外，在动物的研究已显示可能会产生中枢神经系统毒性。^[15]^[16]

禁忌症

个体于第一个孕期（第1到第13周）使用此药物可能会伤害胎儿，不宜使用。^[17]

药物会导致轻度至中毒肝损伤，但无须调整剂量。有严重肝损伤的个体使用时则需谨慎。^[17]

药物交互作用

当蒿甲醚与抗艾滋病药物洛匹那韦/利托那韦一起使用时，会导致血浆中的蒿甲醚水平较低。^[16]与依法韦仑（治疗和预防艾滋病药物）或奈韦拉平（预防艾滋病药物）同时使用也会降低蒿甲醚于血浆中的浓度。^[18]^[19]

蒿甲醚/苯芴醇复方剂不应与抑制细胞色素CYP3A4的药物一起使用。^[1]^[20]

激素避孕药与蒿甲醚/苯芴醇一起使用时，避孕效果会被降低。^[20]

药理学

作用机转

青蒿素类药物的作用机转可能是透过抑制钙离子三磷酸腺苷酶（英语：PfATP6）（PfATP6）而发挥原虫杀伤作用。由于PfATP6是一种调节细胞钙浓度的酶，其功能失调会导致细胞内钙积累，最终细胞因而死亡。^[21]

药物动力学

使用此药物，而同时进行饮食，可将药物的吸收率提高2至3倍。它会与蛋白质高度结合（95.4%）。给药2小时后出现蒿甲醚的最大血药浓度。^[3]

蒿甲醚在人体内主要经由肝脏酵素CYP3A4/CYP3A5（英语：CYP3A5）代谢为活性代谢产物 - 二氢青蒿素。^[3]蒿甲醚母体药物和活性代谢物的生物半衰期约为2小时。^[3]

化学

蒿甲醚是青蒿素的甲醚衍生物，青蒿素是从抗疟疾植物黄花蒿中分离出的一种含过氧化物的内酯。它也被称为二氢青蒿素甲醚，其国际化联名称为(+)-(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-环氧-12H-吡喃(4,3-j)-1,2-苯并二氧杂环己烷。此药物是一种相对亲脂性和不稳定的药物，^[22]此药物除会影响疟原虫的膜运输系统外，也会产生反应性自由基以攻击疟原虫的细胞结构而发挥作用。^[14]

历史

青蒿素是一种极佳的疟疾治疗药物。然而多年来的供应一直不稳定。该药物的唯一来源是生长在东南亚的黄花蒿，但生产循着一种恶性循环模式进行。农民仅在价格高时才愿意种植，不可避免的会供过于求而导致价格下跌，之后产量下降，再次将价格推高。总部位于法国巴黎的赛诺菲制药曾于2013年推出合成法制造，但生产成本不敌种植黄花蒿生产的。目前制药界正致力，试图由黄花蒿中萃取更多的青蒿素及其衍生物。^[23]

参考文献

^ ^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. （原始内容存档于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. （原始内容存档于2017-09-10）.
^ Treatment Of Uncomplicated Malaria Caused By P. vivax, P. ovale, P. malariae or P. knowlesi. World Health Organization. 2015-01-01. （原始内容存档于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]. （原始内容存档于2017-02-23）.
^ WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition: Protozoa: Malaria: Artemether. apps.who.int. [2016-11-09]. （原始内容存档于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. （原始内容存档于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. （原始内容存档于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. （原始内容存档于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]. （原始内容存档于2017-02-23）.

[15] WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition: Protozoa: Malaria: Artemether. apps.who.int. [2016-11-09]. （原始内容存档于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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