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阿尼芬净

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阿尼芬净
临床资料
读音/ˌnɪdjʊləˈfʌnɪn/ ay-NID-yuu-lə-FUN-jin
商品名英语Drug nomenclatureEraxis、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]
1-[(4R,5R)-4,5-Dihydroxy-N2-[[4''-(pentyloxy)[1',1':4',1''-terphenyl]-4-yl]carbonyl]-L-ornithine]echinocandin B[2]
AHFS/Drugs.comMonograph
核准状况
给药途径静脉注射
ATC码
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
  • 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  checkY
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
ECHA InfoCard100.184.856 编辑维基数据链接
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
  • 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=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 checkY
  • Key:JHVAMHSQVVQIOT-QZNDWXLFSA-N checkY

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:

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。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. ^ 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. ^ 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可免费查阅. PMID 15155194. doi:10.1128/AAC.48.6.2021-2024.2004. 
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  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可免费查阅. 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可免费查阅. PMID 28115858. doi:10.2147/CEOR.S122177可免费查阅. 
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  9. ^ ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS (PDF). European Medicines Agency. [2024-07-11]. 
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