阿尼芬淨

**阿尼芬淨**
臨床資料
读音	/eɪˌnɪdjʊləˈfʌndʒɪn/ ay-NID-yuu-lə-FUN-jin
商品名（英语：Drug nomenclature）	Eraxis、Ecalta
其他名稱	(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
核准狀況	歐 EMA: yes; 美 FDA: Anidulafungin;
给药途径	靜脈注射
ATC碼	J02AX06 (WHO) ;
法律規範狀態
法律規範	处方药（℞-only）;
藥物動力學數據
生物利用度	100% (靜脈注射)
血漿蛋白結合率	廣泛 (>99%)
药物代谢	尚未觀察到經由肝臟代謝
生物半衰期	27小時，40–50小時 (完全排除)
排泄途徑	糞便 (~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 ;

阿尼芬淨（英語：Anidulafungin）^[1]^:42以商品商名Eraxis、Ecalta於市面販售，是一種半合成棘白菌素（英语：echinocandin）抗真菌藥。它之前的名稱為LY303366^[3]^[4]^[5]。此藥物與伏立康唑（英语：voriconazole）聯合使用時，也可用於治療侵襲性麴黴屬感染^[6]。它是棘白菌素類抗真菌藥家族中的一員，經由抑制β-葡聚醣合成酶（一種對真菌細胞壁合成很重要的酵素）而發揮作用^[7]。

阿尼芬淨經由靜脈注射方式給藥。^[8]

對懷孕兔子施用阿尼芬淨，曾觀察到對所懷胎兒有輕微的發育影響。對人類的潛在風險尚不清楚，但不推薦個體在懷孕期間使用^[9]^[10]。對於採母乳哺育的個體，在嬰兒的影響尚不清楚，除非對母體的益處高於風險，否則不建議使用^[10]。

此藥物已被列入世界衛生組織基本藥物標準清單之中^[11]。

適應症

阿尼芬淨適用於下列病症的治療：

念珠菌血症（英语：Candidemia）和其他形式的侵襲性念珠菌屬感染（腹內膿瘍和腹膜炎）
食道念珠菌病（英语：Esophageal candidiasis）

目前尚未對使用阿尼芬淨治療念珠菌引起的心內膜炎、骨髓炎和腦膜炎進行過研究，也尚未對足夠數量的嗜中性白血球低下患者進行研究，以確定藥物對此類疾病的療效^[2]。

副作用

使用後通常的副作用有：肝功能測試異常數值、飢餓感、流汗、煩躁及頭暈等。嚴重的副作用有蕁麻疹、呼吸困難及臉部、嘴唇、舌頭或喉嚨腫脹等^[12]^[10]。

禁忌症

對於阿尼芬淨（或藥物組成物）或是棘白菌素過敏的個體禁止使用。具有已知，或是疑似有遺傳性果糖不耐症的個體也禁止使用^[12]。

與其他藥物交互作用

阿尼芬淨除與布拉酵母菌（一種益生菌）會有嚴重的交互作用，與伏環孢素（英语：voclosporin）有溫和交互作用外，通常不與其他藥物發生交互作用^[12]。

藥理學

藥效學

阿尼芬淨與其他抗真菌藥物顯著不同，因為它在使用者身體pH值和體溫下會發生化學降解，形成無活性形式。由於它不會被體內的酶降解，或是經由肝臟或腎臟排泄，因此任何程度的肝或腎功能不全的患者均可安全使用^[13]。

參數數值分佈體積 (升) 30–50升^[14] 血漿蛋白結合 (%) 99%^[14] 生物半衰期 [小時] 24小時^[14]

藥物動力學

阿尼芬淨顯然不被肝臟代謝。這種特定藥物經歷緩慢的化學水解，形成缺乏抗真菌活性的開環肽。藥物的生物半衰期為27小時。約30%經由糞便排出（10%以原藥形式）。不到1%經由尿液排出^[15]^[16]^[17]。

作用機轉

阿尼芬淨抑制β-葡聚醣合成酶，這種酶對於形成 (1→3)-β-D-葡聚醣（真菌細胞壁的主要成分）有重要作用。哺乳動物細胞中不存在β-葡聚醣合成酶，真菌的此種酶即成為藥物抗真菌活性的標靶^[18]。

半合成過程

阿尼芬淨是一種半合成抗真菌藥物。其生產原料為棘白菌素B (echinocandin B，為一種由小巢狀麴菌或近緣種粗糙曲霉菌（英语：Aspergillus rugulosus）發酵產生的脂肽（英语：lipopeptide）。棘白菌素B首先會經過來自猶他游動放線菌（英语：Actinoplanes utahensis）的去酰化酶作用，切割掉其亞麻油酰側鏈 (linoleoyl side chain) 的過程稱為去酰化 (deacylation)。^[19]接着經過一系列包含化學酰化反應 (chemical reacylation) 在内的三個合成步骤，最终得此種抗真菌藥^[18]^[20]。

歷史

阿尼芬淨最初由兩位於禮來藥業服務的研究人員特納（Turner）和德博諾（Debono ）發現，之後授權給名為Vicuron Pharmaceuticals的美國藥業，後者將藥物提交美國食品藥物管理局（FDA）申請用於醫療用途^[21]。輝瑞藥業在2005年秋季併購Vicuron Pharmaceuticals，並取得此藥物的權利^[22]，最終於2006年2月21日獲得FDA的核准^[23]。

參考文獻

^ ^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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