阿尼芬净

**阿尼芬净**
临床资料
读音	/eɪˌnɪdjʊləˈfʌndʒɪn/ ay-NID-yuu-lə-FUN-jin
商品名（英语：Drug nomenclature）	Eraxis、Ecalta
其他名称	(4R,5S)-4,5-Dihydroxy-N2-[[4''-(pentyloxy)-p-terphenyl-4-yl]carbonyl]-L-ornithyl-L-threonyl-trans-4-hydroxy-L-prolyl-(S)-4-hydroxy-4-(p-hydroxyphenyl)-L-threonyl-L-threonyl-(3S,4S)-3-hydroxy-4-methyl-L-proline cyclic (6→1)-peptide; 1-[(4R,5R)-4,5-Dihydroxy-N2-[[4''-(pentyloxy)[1',1':4',1''-terphenyl]-4-yl]carbonyl]-L-ornithine]echinocandin B
AHFS/Drugs.com	Monograph
核准状况	欧 EMA: yes; 美 FDA: Anidulafungin;
给药途径	静脉注射
ATC码	J02AX06 (WHO) ;
法律规范状态
法律规范	处方药（℞-only）;
药物动力学数据
生物利用度	100% (静脉注射)
血浆蛋白结合率	广泛 (>99%)
药物代谢	尚未观察到经由肝脏代谢
生物半衰期	27小时，40–50小时 (完全排除)
排泄途径	粪便 (~30%), 尿液 (<1%)
识别信息
	IUPAC命名法 N-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-6-[(1S,2R)-1,2-Dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.09,13]heptacosan-18-yl]- 4-{4-[4-(pentyloxy)phenyl]phenyl}benzamide; ;
CAS号	166663-25-8
PubChem CID	166548;
DrugBank	DB00362 ;
ChemSpider	21106258 ;
UNII	9HLM53094I;
KEGG	D03211 ;
ChEBI	CHEBI:55346 ;
ChEMBL	ChEMBL1630215 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID50873201 ;
ECHA InfoCard	100.184.856
化学信息
化学式	C58H73N7O17
摩尔质量	1,140.25 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES CCCCCOc1ccc(cc1)c2ccc(cc2)c3ccc(cc3)C(=O)N[C@H]6C[C@@H](O)[C@@H](O)NC(=O)C4[C@@H](O)[C@@H](C)CN4C(=O)C(NC(=O)C(NC(=O)C5C[C@@H](O)CN5C(=O)C(NC6=O)[C@@H](C)O)[C@@H](O)[C@H](O)c7ccc(O)cc7)[C@@H](C)O;
	InChI InChI=1S/C58H73N7O17/c1-5-6-7-24-82-40-22-18-35(19-23-40)33-10-8-32(9-11-33)34-12-14-37(15-13-34)51(74)59-41-26-43(70)54(77)63-56(79)47-48(71)29(2)27-65(47)58(81)45(31(4)67)61-55(78)46(50(73)49(72)36-16-20-38(68)21-17-36)62-53(76)42-25-39(69)28-64(42)57(80)44(30(3)66)60-52(41)75/h8-23,29-31,39,41-50,54,66-73,77H,5-7,24-28H2,1-4H3,(H,59,74)(H,60,75)(H,61,78)(H,62,76)(H,63,79)/t29-,30+,31+,39+,41-,42?,43+,44?,45?,46?,47?,48-,49+,50+,54+/m0/s1 ; Key:JHVAMHSQVVQIOT-QZNDWXLFSA-N ;

阿尼芬净（英语：Anidulafungin）^[1]^:42以商品商名Eraxis、Ecalta于市面贩售，是一种半合成棘白菌素（英语：echinocandin）抗真菌药。它之前的名称为LY303366^[3]^[4]^[5]。此药物与伏立康唑（英语：voriconazole）联合使用时，也可用于治疗侵袭性曲霉属感染^[6]。它是棘白菌素类抗真菌药家族中的一员，经由抑制β-葡聚糖合成酶（一种对真菌细胞壁合成很重要的酵素）而发挥作用^[7]。

阿尼芬净经由静脉注射方式给药。^[8]

对怀孕兔子施用阿尼芬净，曾观察到对所怀胎儿有轻微的发育影响。对人类的潜在风险尚不清楚，但不推荐个体在怀孕期间使用^[9]^[10]。对于采母乳哺育的个体，在婴儿的影响尚不清楚，除非对母体的益处高于风险，否则不建议使用^[10]。

此药物已被列入世界卫生组织基本药物标准清单之中^[11]。

适应症

阿尼芬净适用于下列病症的治疗：

念珠菌血症（英语：Candidemia）和其他形式的侵袭性念珠菌属感染（腹内脓疡和腹膜炎）
食道念珠菌病（英语：Esophageal candidiasis）

目前尚未对使用阿尼芬净治疗念珠菌引起的心内膜炎、骨髓炎和脑膜炎进行过研究，也尚未对足够数量的嗜中性白血球低下患者进行研究，以确定药物对此类疾病的疗效^[2]。

副作用

使用后通常的副作用有：肝功能测试异常数值、饥饿感、流汗、烦躁及头晕等。严重的副作用有荨麻疹、呼吸困难及脸部、嘴唇、舌头或喉咙肿胀等^[12]^[10]。

禁忌症

对于阿尼芬净（或药物组成物）或是棘白菌素过敏的个体禁止使用。具有已知，或是疑似有遗传性果糖不耐症的个体也禁止使用^[12]。

与其他药物交互作用

阿尼芬净除与布拉酵母菌（一种益生菌）会有严重的交互作用，与伏环孢素（英语：voclosporin）有温和交互作用外，通常不与其他药物发生交互作用^[12]。

药理学

药效学

阿尼芬净与其他抗真菌药物显著不同，因为它在使用者身体pH值和体温下会发生化学降解，形成无活性形式。由于它不会被体内的酶降解，或是经由肝脏或肾脏排泄，因此任何程度的肝或肾功能不全的患者均可安全使用^[13]。

参数数值分布体积 (升) 30–50升^[14] 血浆蛋白结合 (%) 99%^[14] 生物半衰期 [小时] 24小时^[14]

药物动力学

阿尼芬净显然不被肝脏代谢。这种特定药物经历缓慢的化学水解，形成缺乏抗真菌活性的开环肽。药物的生物半衰期为27小时。约30%经由粪便排出（10%以原药形式）。不到1%经由尿液排出^[15]^[16]^[17]。

作用机转

阿尼芬净抑制β-葡聚糖合成酶，这种酶对于形成 (1→3)-β-D-葡聚糖（真菌细胞壁的主要成分）有重要作用。哺乳动物细胞中不存在β-葡聚糖合成酶，真菌的此种酶即成为药物抗真菌活性的标靶^[18]。

半合成过程

阿尼芬净是一种半合成抗真菌药物。其生产原料为棘白菌素B (echinocandin B，为一种由小巢状麹菌或近缘种粗糙曲霉菌（英语：Aspergillus rugulosus）发酵产生的脂肽（英语：lipopeptide）。棘白菌素B首先会经过来自犹他游动放线菌（英语：Actinoplanes utahensis）的去酰化酶作用，切割掉其亚麻油酰侧链 (linoleoyl side chain) 的过程称为去酰化 (deacylation)。^[19]接着经过一系列包含化学酰化反应 (chemical reacylation) 在内的三个合成步骤，最终得此种抗真菌药^[18]^[20]。

历史

阿尼芬净最初由两位于礼来药业服务的研究人员特纳（Turner）和德博诺（Debono ）发现，之后授权给名为Vicuron Pharmaceuticals的美国药业，后者将药物提交美国食品药物管理局（FDA）申请用于医疗用途^[21]。辉瑞药业在2005年秋季并购Vicuron Pharmaceuticals，并取得此药物的权利^[22]，最终于2006年2月21日获得FDA的核准^[23]。

参考文献

^ ^1.0 ^1.1 International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary names: List 43 (PDF). World Health Organization. 2000 [11 November 2016].
^ ^2.0 ^2.1 Eraxis (anidulafungin) for Injection, for Intravenous Use. Full Prescribing Information. Roerig (Division of Pfizer, Inc.), New York, NY 10017. [2016-11-11].
^ Krause DS, Reinhardt J, Vazquez JA, Reboli A, Goldstein BP, Wible M, Henkel T. Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia. Antimicrobial Agents and Chemotherapy. June 2004, 48 (6): 2021–2024. PMC 415613 . PMID 15155194. doi:10.1128/AAC.48.6.2021-2024.2004.
^ Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. In vitro activities of anidulafungin against more than 2,500 clinical isolates of Candida spp., including 315 isolates resistant to fluconazole. Journal of Clinical Microbiology. November 2005, 43 (11): 5425–5427. PMC 1287823 . PMID 16272464. doi:10.1128/JCM.43.11.5425-5427.2005.
^ Pfaller MA, Diekema DJ, Boyken L, Messer SA, Tendolkar S, Hollis RJ, Goldstein BP. Effectiveness of anidulafungin in eradicating Candida species in invasive candidiasis. Antimicrobial Agents and Chemotherapy. November 2005, 49 (11): 4795–4797. PMC 1280139 . PMID 16251335. doi:10.1128/AAC.49.11.4795-4797.2005.
^ Grau S, Azanza JR, Ruiz I, Vallejo C, Mensa J, Maertens J, Heinz WJ, Barrueta JA, Peral C, Mesa FJ, Barrado M, Charbonneau C, Rubio-Rodríguez D, Rubio-Terrés C. Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain. ClinicoEconomics and Outcomes Research. January 2017, 9: 39–47. PMC 5221484 . PMID 28115858. doi:10.2147/CEOR.S122177 .
^ Zida A, Bamba S, Yacouba A, Ouedraogo-Traore R, Guiguemdé RT. Anti-Candida albicans natural products, sources of new antifungal drugs: A review. Journal de Mycologie Médicale. March 2017, 27 (1): 1–19. PMID 27842800. doi:10.1016/j.mycmed.2016.10.002.
^ HIGHLIGHTS OF PRESCRIBING INFORMATION for ERAXIS. (PDF). Pfizer. [2024-0726].
^ ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS (PDF). European Medicines Agency. [2024-07-11].
^ ^10.0 ^10.1 ^10.2 Anidulafungin Pregnancy and Breastfeeding Warnings. Drugs.com. 2023-10-30 [2024-07-11].
^ World Health Organization. World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. 2021. hdl:10665/345533 . WHO/MHP/HPS/EML/2021.02.
^ ^12.0 ^12.1 ^12.2 Anidulafungin. RxList. 2023-10-30 [2024-07-11].
^ Eraxis. RxList. 2009-06-24 [2009-08-01].
^ ^14.0 ^14.1 ^14.2 Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis: review of the literature. European Journal of Medical Research. April 2011, 16 (4): 159–166. PMC 3352072 . PMID 21486730. doi:10.1186/2047-783x-16-4-159 .
^ Trissel LA, Ogundele AB. Compatibility of anidulafungin with other drugs during simulated Y-site administration. American Journal of Health-System Pharmacy. April 2005, 62 (8): 834–837. PMID 15821277. doi:10.1093/ajhp/62.8.834 .
^ Vazquez JA. Anidulafungin: a new echinocandin with a novel profile. Clinical Therapeutics. June 2005, 27 (6): 657–673. PMID 16117974. doi:10.1016/j.clinthera.2005.06.010.
^ Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America (PDF). Clinical Infectious Diseases. February 2008, 46 (3): 327–360. PMID 18177225. S2CID 8789905. doi:10.1086/525258.
^ ^18.0 ^18.1 Denning DW. Echinocandins and pneumocandins--a new antifungal class with a novel mode of action. The Journal of Antimicrobial Chemotherapy. November 1997, 40 (5): 611–614. PMID 9421307. doi:10.1093/jac/dkf045 .
^ Shao L, Li J, Liu A, Chang Q, Lin H, Chen D. Efficient bioconversion of echinocandin B to its nucleus by overexpression of deacylase genes in different host strains. Applied and Environmental Microbiology. February 2013, 79 (4): 1126–1133. Bibcode:2013ApEnM..79.1126S. PMC 3568618 . PMID 23220968. doi:10.1128/AEM.02792-12.
^ Anidulafungin (PDF). EMA Europa. 2007.
^ Vicuron Pharmaceuticals Files New Drug Application (NDA) for Anidulafungin for Treatment of Invasive Candidiasis/Candidemia. PRNewswire. 2005-08-18. （原始内容存档于2012-05-16）.
^ Vicuron Pharmaceuticals Stockholders Approve Merger With Pfizer. PRNewswire. 2005-08-15. （原始内容存档于2012-05-16）.
^ FDA Approves New Treatment for Fungal Infections. FDA News Release. Food and Drug Administration. 2006-02-21 [2009-08-01]. （原始内容存档于2009-07-10）.

[INN-1] 1.0 ^1.1 International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary names: List 43 (PDF). World Health Organization. 2000 [11 November 2016].

[PI-2] 2.0 ^2.1 Eraxis (anidulafungin) for Injection, for Intravenous Use. Full Prescribing Information. Roerig (Division of Pfizer, Inc.), New York, NY 10017. [2016-11-11].

[3] Krause DS, Reinhardt J, Vazquez JA, Reboli A, Goldstein BP, Wible M, Henkel T. Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia. Antimicrobial Agents and Chemotherapy. June 2004, 48 (6): 2021–2024. PMC 415613 . PMID 15155194. doi:10.1128/AAC.48.6.2021-2024.2004.

[4] Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. In vitro activities of anidulafungin against more than 2,500 clinical isolates of Candida spp., including 315 isolates resistant to fluconazole. Journal of Clinical Microbiology. November 2005, 43 (11): 5425–5427. PMC 1287823 . PMID 16272464. doi:10.1128/JCM.43.11.5425-5427.2005.

[5] Pfaller MA, Diekema DJ, Boyken L, Messer SA, Tendolkar S, Hollis RJ, Goldstein BP. Effectiveness of anidulafungin in eradicating Candida species in invasive candidiasis. Antimicrobial Agents and Chemotherapy. November 2005, 49 (11): 4795–4797. PMC 1280139 . PMID 16251335. doi:10.1128/AAC.49.11.4795-4797.2005.

[6] Grau S, Azanza JR, Ruiz I, Vallejo C, Mensa J, Maertens J, Heinz WJ, Barrueta JA, Peral C, Mesa FJ, Barrado M, Charbonneau C, Rubio-Rodríguez D, Rubio-Terrés C. Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain. ClinicoEconomics and Outcomes Research. January 2017, 9: 39–47. PMC 5221484 . PMID 28115858. doi:10.2147/CEOR.S122177 .

[7] Zida A, Bamba S, Yacouba A, Ouedraogo-Traore R, Guiguemdé RT. Anti-Candida albicans natural products, sources of new antifungal drugs: A review. Journal de Mycologie Médicale. March 2017, 27 (1): 1–19. PMID 27842800. doi:10.1016/j.mycmed.2016.10.002.

[8] HIGHLIGHTS OF PRESCRIBING INFORMATION for ERAXIS. (PDF). Pfizer. [2024-0726].

[9] ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS (PDF). European Medicines Agency. [2024-07-11].

[Drugs.com-10] 10.0 ^10.1 ^10.2 Anidulafungin Pregnancy and Breastfeeding Warnings. Drugs.com. 2023-10-30 [2024-07-11].

[WHO22nd-11] World Health Organization. World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. 2021. hdl:10665/345533 . WHO/MHP/HPS/EML/2021.02.

[RxList-12] 12.0 ^12.1 ^12.2 Anidulafungin. RxList. 2023-10-30 [2024-07-11].

[13] Eraxis. RxList. 2009-06-24 [2009-08-01].

[Kofla_2011-14] 14.0 ^14.1 ^14.2 Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis: review of the literature. European Journal of Medical Research. April 2011, 16 (4): 159–166. PMC 3352072 . PMID 21486730. doi:10.1186/2047-783x-16-4-159 .

[pmid15821277-15] Trissel LA, Ogundele AB. Compatibility of anidulafungin with other drugs during simulated Y-site administration. American Journal of Health-System Pharmacy. April 2005, 62 (8): 834–837. PMID 15821277. doi:10.1093/ajhp/62.8.834 .

[pmid16117974-16] Vazquez JA. Anidulafungin: a new echinocandin with a novel profile. Clinical Therapeutics. June 2005, 27 (6): 657–673. PMID 16117974. doi:10.1016/j.clinthera.2005.06.010.

[pmid18177225-17] Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America (PDF). Clinical Infectious Diseases. February 2008, 46 (3): 327–360. PMID 18177225. S2CID 8789905. doi:10.1086/525258.

[pmid9421307-18] 18.0 ^18.1 Denning DW. Echinocandins and pneumocandins--a new antifungal class with a novel mode of action. The Journal of Antimicrobial Chemotherapy. November 1997, 40 (5): 611–614. PMID 9421307. doi:10.1093/jac/dkf045 .

[19] Shao L, Li J, Liu A, Chang Q, Lin H, Chen D. Efficient bioconversion of echinocandin B to its nucleus by overexpression of deacylase genes in different host strains. Applied and Environmental Microbiology. February 2013, 79 (4): 1126–1133. Bibcode:2013ApEnM..79.1126S. PMC 3568618 . PMID 23220968. doi:10.1128/AEM.02792-12.

[urlAnidulafungin-20] Anidulafungin (PDF). EMA Europa. 2007.

[21] Vicuron Pharmaceuticals Files New Drug Application (NDA) for Anidulafungin for Treatment of Invasive Candidiasis/Candidemia. PRNewswire. 2005-08-18. （原始内容存档于2012-05-16）.

[22] Vicuron Pharmaceuticals Stockholders Approve Merger With Pfizer. PRNewswire. 2005-08-15. （原始内容存档于2012-05-16）.

[23] FDA Approves New Treatment for Fungal Infections. FDA News Release. Food and Drug Administration. 2006-02-21 [2009-08-01]. （原始内容存档于2009-07-10）.

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