用户:ThomasYehYeh/沙盒/伊朗罪案

ThomasYehYeh/沙盒/伊朗罪案
组成
青蒿琥酯	抗疟药
咯萘啶	抗疟药
临床资料
商品名（英语：Drug nomenclature）	Pyramax
其他名称	Artesunate/pyronaridine tetraphosphate
给药途径	口服给药
ATC码	P01BF06 (WHO) ;
识别信息
CAS号	884661-13-6

青蒿琥酯/咯萘啶（英语：artesunate/pyronaridine）以Pyramax品牌于市面上销售，它含有两种治疗疟疾的药物 - 青蒿琥酯和咯萘啶 - 是一种用于治疗疟疾的复方药。^[3]^[1]它可用于治疗恶性疟原虫和间日疟原虫导致的疟疾。^[3]此药物透过口服方式给药。^[2]

人体对于此药物通常具有良好的耐受性。使用后的副作用有头痛、呕吐或咳嗽。^[1]不建议患有严重肝病或肾病变的个体使用。^[1]一般不建议在个体怀孕初期使用，避免对于胎儿造成伤害。但当没其他选择，而治疗可挽救母亲的生命时，则可使用。^[2]^[4]药物中的两种成分透过不同的机制而发挥作用。^[2]

此药物已被列入世界卫生组织基本药物标准清单之中。^[3]

医疗用途

青蒿琥酯/咯萘啶用于治疗恶性疟原虫和间日疟原虫型导致的疟疾疟疾。不建议用于治疗病情严重的患者。^[2]

根据一篇发表于2019年的综述（于2021年更新），说明此复方药与复方蒿甲醚（又称蒿甲醚/苯芴醇]]同样有效。^[5]与美尔奎宁和青蒿琥酯联合使用的疗效也相似。不建议用青蒿琥酯/咯萘啶于预防疟疾之用。^[2]

特定群体

怀孕

不建议在个体怀孕的第一期使用青蒿琥酯/咯萘啶治疗疟疾。但如果认为治疗对母亲的生命极为重要，且无其他适合的抗疟药可用时则不应拒绝使用。^[4]

母乳哺育

根据在大鼠的研究，显示此药物会分泌到乳汁中。应对母乳哺育的好处与婴儿可能因母乳中含有咯萘啶而产生的风险进行权衡。^[4]

儿童

临床试验结果显示，每日一次、连续三天服用儿科青蒿琥酯/咯萘啶颗粒以治疗儿童疟疾，不仅耐受性良好，临床疗效亦显著。在实际医疗状况中亦证实此药物的有效性。^[6]

年长者

临床研究并未包括65岁及以上的患者。根据目前所知和短暂的3日疗程，尚不需根据年龄调整剂量。但考虑到肝肾功能可能随年龄下降，年长者使用本产品时应谨慎。^[4]

禁忌症

对此药物的禁忌症有：^[4]

已知对药物成分或制剂中任何成分过敏者。
罹患临床体征或症状的肝损伤（如恶心和/或腹痛且有黄疸）者。
已知严重肝病（即失代偿性肝硬化，Child-Pugh分级系统被列为B（肝功能中度衰竭）或C（肝功能严重衰竭）的阶段）者。
严重肾功能障碍者

交互作用

建议在以下情况下须特别谨慎：^[4]

与已知和线粒体毒性（英语：mitochondrial toxicity）相关的药物（如丙戊酸，抗反转录病毒药物）、药用植物以及扑热息痛合用。

作用机转

青蒿琥酯的作用机转仍未被完全了解，且有争议。它是一种前体药物，可迅速转化为具活性形式的双氢青蒿素 (DHA)。过程涉及透过血浆酯酶水解4-碳酯基。^[7]推测DHA药效团中内过氧化物桥的裂解会产生活性氧 (ROS)，而增加氧化压力并透过烷基化引起疟原虫蛋白损伤。此外，青蒿琥酯还可有效抑制重要的恶性疟原虫外运蛋白1 (EXP1) - 一种膜谷胱甘肽S-转移酶（MAPEG家族）。^[8]青蒿素于2016年已被证明可与大量标靶结合，显示它有混杂的作用方式。^[9]有证据显示DHA抑制内质膜上的钙依赖性ATP酶，而破坏寄生虫的蛋白质折叠。^[7]而在咯萘啶方面 - 疟原虫首先在肝细胞中生长和繁殖，然后进入血液，侵入红血球并进行另一次复制。疟原虫在感染的红血球中于其食物空泡中消化血红素，导致血红素释放。游离血红素对疟原虫有毒性，而疟原虫随后通过二聚化和聚合将血红素转化为疟色素并经解毒过程将其隔离。随着疟原虫发育，疟色素会释放进入宿主血液循环中，诱导发炎反应，引起疾病临床表现。咯萘啶靶向血红素并以1:2的化学计量形成药物-血红素复合体。这种作用可抑制血红素聚合/结晶为疟色素，并干扰疟原虫在消化空泡中的血红素解毒过程。宿主的游离血红素的水平因而升高，促进过氧化反应并导致疟原虫死亡。^[10]

药物再利用研究

有些in vitro（体外试验）证据显示青蒿琥酯/咯萘啶可能值得进行临床试验，以确定它是否可作为治疗COVID-19的药物。^[11]

参考文献

^ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 Application for inclusion in the WHO Model List of essential medicines (PDF). WHO. Nov 2010 [2017-06-29].
^ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 Pyramax 180 mg/60 mg Film-coated tablet (PDF). EMA. [2017-12-13]. （原始内容 (PDF)存档于2017-12-14）.
^ ^3.0 ^3.1 ^3.2 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.
^ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 Pyramax, INN - pyronaridine tetraphosphate /artesunate (PDF). Shin Poong Pharmaceutical Co., Ltd. [2024-09-29].
^ Pryce J, Taylor M, Fox T, Hine P. Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria. The Cochrane Database of Systematic Reviews. June 2022, 2022 (6): CD006404. PMC 9209011 . PMID 35726133. doi:10.1002/14651858.CD006404.pub4.
^ Ramharter, Michael; Djimde, Abdoulaye A. Safety and efficacy of pyronaridine–artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study. Malaria Journal. 2024-02-28, 23 (61 (2024)) [2024-09-29]. doi:10.1186/s12936-024-04885-3.
^ ^7.0 ^7.1 Cui L, Su XZ. Discovery, mechanisms of action and combination therapy of artemisinin. Expert Review of Anti-Infective Therapy. October 2009, 7 (8): 999–1013. PMC 2778258 . PMID 19803708. doi:10.1586/eri.09.68.
^ Lisewski AM, Quiros JP, Ng CL, Adikesavan AK, Miura K, Putluri N, et al. Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate. Cell. August 2014, 158 (4): 916–928. PMC 4167585 . PMID 25126794. doi:10.1016/j.cell.2014.07.011.
^ Wang J, Zhang CJ, Chia WN, Loh CC, Li Z, Lee YM, et al. Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nature Communications. December 2015, 6: 10111. Bibcode:2015NatCo...610111W. PMC 4703832 . PMID 26694030. doi:10.1038/ncomms10111.
^ Chu, Wan-Yu; Dorlo, Thomas P C. Pyronaridine: a review of its clinical pharmacology in the treatment of malaria. Journal of Antimicrobial Chemotherapy. 2023-08-28, 78 (10): 2406–2418 [2024-09-29]. doi:10.1093/jac/dkad260.
^ Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, et al. Repurposing Antimalarials to Tackle the COVID-19 Pandemic. Trends in Parasitology. January 2021, 37 (1): 8–11. PMC 7572038 . PMID 33153922. doi:10.1016/j.pt.2020.10.003.

[WHO2010-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 Application for inclusion in the WHO Model List of essential medicines (PDF). WHO. Nov 2010 [2017-06-29].

[EMA2017-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 Pyramax 180 mg/60 mg Film-coated tablet (PDF). EMA. [2017-12-13]. （原始内容 (PDF)存档于2017-12-14）.

[WHO21st-3] 3.0 ^3.1 ^3.2 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.

[Shin_Poong-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 Pyramax, INN - pyronaridine tetraphosphate /artesunate (PDF). Shin Poong Pharmaceutical Co., Ltd. [2024-09-29].

[:0-5] Pryce J, Taylor M, Fox T, Hine P. Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria. The Cochrane Database of Systematic Reviews. June 2022, 2022 (6): CD006404. PMC 9209011 . PMID 35726133. doi:10.1002/14651858.CD006404.pub4.

[6] Ramharter, Michael; Djimde, Abdoulaye A. Safety and efficacy of pyronaridine–artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study. Malaria Journal. 2024-02-28, 23 (61 (2024)) [2024-09-29]. doi:10.1186/s12936-024-04885-3.

[Cui2009-7] 7.0 ^7.1 Cui L, Su XZ. Discovery, mechanisms of action and combination therapy of artemisinin. Expert Review of Anti-Infective Therapy. October 2009, 7 (8): 999–1013. PMC 2778258 . PMID 19803708. doi:10.1586/eri.09.68.

[8] Lisewski AM, Quiros JP, Ng CL, Adikesavan AK, Miura K, Putluri N, et al. Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate. Cell. August 2014, 158 (4): 916–928. PMC 4167585 . PMID 25126794. doi:10.1016/j.cell.2014.07.011.

[9] Wang J, Zhang CJ, Chia WN, Loh CC, Li Z, Lee YM, et al. Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nature Communications. December 2015, 6: 10111. Bibcode:2015NatCo...610111W. PMC 4703832 . PMID 26694030. doi:10.1038/ncomms10111.

[10] Chu, Wan-Yu; Dorlo, Thomas P C. Pyronaridine: a review of its clinical pharmacology in the treatment of malaria. Journal of Antimicrobial Chemotherapy. 2023-08-28, 78 (10): 2406–2418 [2024-09-29]. doi:10.1093/jac/dkad260.

[11] Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, et al. Repurposing Antimalarials to Tackle the COVID-19 Pandemic. Trends in Parasitology. January 2021, 37 (1): 8–11. PMC 7572038 . PMID 33153922. doi:10.1016/j.pt.2020.10.003.

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