泊沙康唑

泊沙康唑
臨床資料
商品名（英语：Drug nomenclature）	Noxafil, Posanol, others
AHFS/Drugs.com	Monograph
MedlinePlus	a607036
核准狀況	歐 EMA: yes; 美 DailyMed: Posaconazole;
懷孕分級	澳: B3 ; ;
给药途径	口服，静脉注射
ATC碼	J02AC04 (WHO) ;
法律規範狀態
法律規範	澳：限医生处方（S4）; 加：处方药（℞-only）; 中：处方药 ; 歐：Rx-only; 英：处方药（℞-only） (POM); 美：处方药（℞-only）;
藥物動力學數據
生物利用度	低（口服8–47%）
血漿蛋白結合率	98–99%
药物代谢	肝脏 (葡萄糖醛酸化（英语：glucuronidation）)
生物半衰期	16–31 小时
排泄途徑	粪便（71–77%）和肾脏（13–14%）
识别信息
	IUPAC命名法 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2- hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one; ;
CAS号	171228-49-2
PubChem CID	147912;
DrugBank	DB01263 ;
ChemSpider	130409 ;
UNII	6TK1G07BHZ;
KEGG	D02555 ;
ChEBI	CHEBI:64355 ;
ChEMBL	ChEMBL1397 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID6049066 ;
ECHA InfoCard	100.208.201
化学信息
化学式	C37H42F2N8O4
摩尔质量	700.79 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C1N(/N=C\N1c2ccc(cc2)N7CCN(c6ccc(OCC3C[C@@](OC3)(c4ccc(F)cc4F)Cn5ncnc5)cc6)CC7)[C@@H](CC)[C@@H](O)C;
	InChI InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27?,35-,37-/m0/s1 ; Key:RAGOYPUPXAKGKH-AGDNISCASA-N ;

泊沙康唑（英語：Posaconazole），商品名诺科飞（英語：Noxafil）等，是一种三唑类抗真菌药^[7]^[8]。

2005年10月，该药物在欧盟被批准用于医疗用途^[6]，2006年9月在美国被批准^[5]^[9]。该药物可作为仿制药使用^[10]^[11]。

医学用途

泊沙康唑用于治疗侵袭性曲霉菌和念珠菌感染^[5]。它也被用于治疗口腔念珠菌病（OPC），包括对伊曲康唑和/或氟康唑治疗有耐药性的OPC^[5]。它还被用于治疗严重免疫缺陷患者的念珠菌、毛黴菌和曲霉菌侵袭性感染^[12]^[13]。

泊沙康唑在治疗鐮刀菌屬引起的侵袭性疾病（镰刀菌病（英语：Fusariosis））方面的临床证据有限^[14]。

在小鼠模型中，泊沙康唑似乎对福氏內格里阿米巴腦膜腦炎有帮助^[15]。

药理学

药效学

泊沙康唑通过破坏磷脂酰基链的紧密堆积，削弱某些膜结合酶系统（如ATP酶和电子传递系统酶）的功能，从而抑制真菌的生长。泊沙康唑通过抑制羊毛甾醇14α-脫甲基酶和甲基化甾醇前体的积累来阻止麦角固醇的合成。泊沙康唑在抑制14α-脫甲基酶方面比伊曲康唑显著地更有效^[5]^[16]^[17]。

微生物学

泊沙康唑对以下微生物具有活性：^[16]^[18]

药代动力学

泊沙康唑在3至5小时内被吸收。它主要通过肝脏消除，半衰期约为35小时。与高脂肪餐一起口服泊沙康唑可使生物利用度超过90%，血药浓度是空腹状态的4倍^[5]^[18] 。

参考来源

^ Posaconazole (Noxafil) Use During Pregnancy. Drugs.com. 2019-04-23 [2020-01-30]. （原始内容存档于2020-01-30）.
^ Posaconazole suspension ARX/Posaconazole TIH/APX-Posaconazole (Arrow Pharma Pty Ltd). Therapeutic Goods Administration (TGA). 2023-02-16 [2023-04-29]. （原始内容存档于2023-03-18）.
^ Posanol Product information. Health Canada. 2012-04-25 [2022-07-03]. （原始内容存档于2021-05-16）.
^ Noxafil 100 mg Gastro-resistant Tablets - Summary of Product Characteristics (SmPC). (emc). 2022-01-10 [2022-07-03]. （原始内容存档于2022-02-24）.
^ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 Noxafil- posaconazole suspension Noxafil- posaconazole tablet, coated Noxafil- posaconazole solution. DailyMed. 2020-03-20 [2020-08-15]. （原始内容存档于2021-02-26）.
^ ^6.0 ^6.1 Noxafil EPAR. European Medicines Agency. 2007-03-28 [2022-07-03]. （原始内容存档于2021-10-19）.
^ Schiller DS, Fung HB. Posaconazole: an extended-spectrum triazole antifungal agent. Clinical Therapeutics. September 2007, 29 (9): 1862–86. PMID 18035188. doi:10.1016/j.clinthera.2007.09.015.
^ Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH. Posaconazole: an oral triazole with an extended spectrum of activity. The Annals of Pharmacotherapy. October 2008, 42 (10): 1429–38 [2008-12-11]. PMID 18713852. S2CID 21777822. doi:10.1345/aph.1L005. ^{[失效連結]}
^ Drug Approval Package: Noxafil (Posaconazole) NDA #022003. U.S. Food and Drug Administration (FDA). 2006-11-09 [2020-08-15]. （原始内容存档于2021-04-03）.
^ Posaconazole: FDA-Approved Drugs. U.S. Food and Drug Administration (FDA). [2020-08-15]. （原始内容存档于2020-10-20）.
^ First Generic Drug Approvals. U.S. Food and Drug Administration. 2022-10-17 [2022-11-28]. （原始内容存档于2021-01-26）.
^ Li X, Brown N, Chau AS, López-Ribot JL, Ruesga MT, Quindos G, et al. Changes in susceptibility to posaconazole in clinical isolates of Candida albicans. The Journal of Antimicrobial Chemotherapy. January 2004, 53 (1): 74–80. PMID 14657086. doi:10.1093/jac/dkh027 .
^ Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clinical Infectious Diseases. January 2007, 44 (1): 2–12. JSTOR 4485188. PMID 17143808. doi:10.1086/508774 .
^ Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, Kontoyiannis DP. Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clinical Infectious Diseases. May 2006, 42 (10): 1398–403. PMID 16619151. doi:10.1086/503425 .
^ Colon BL, Rice CA, Guy RK, Kyle DE. Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis. The Journal of Infectious Diseases. March 2019, 219 (7): 1095–1103. PMC 6420171 . PMID 30358879. doi:10.1093/infdis/jiy622.
^ ^16.0 ^16.1 Brunton L, Lazo J, Parker K. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. San Francisco: McGraw-Hill; 2006. ISBN 978-0-07-142280-2
^ Clinical Pharmacology Posaconazole. [2010-02-18]. （原始内容存档于2021-08-30）.
^ ^18.0 ^18.1 Ashley ED, Perfect JR. Pharmacology of azoles. Kauffman CA (编). UpToDate. Waltham, MA: UpToDate. October 2017 [2010-02-18]. （原始内容存档于2013-02-09）.

外部連結

维基共享资源上的相關多媒體資源：泊沙康唑

[Drugs.com_pregnancy-1] Posaconazole (Noxafil) Use During Pregnancy. Drugs.com. 2019-04-23 [2020-01-30]. （原始内容存档于2020-01-30）.

[2] Posaconazole suspension ARX/Posaconazole TIH/APX-Posaconazole (Arrow Pharma Pty Ltd). Therapeutic Goods Administration (TGA). 2023-02-16 [2023-04-29]. （原始内容存档于2023-03-18）.

[3] Posanol Product information. Health Canada. 2012-04-25 [2022-07-03]. （原始内容存档于2021-05-16）.

[4] Noxafil 100 mg Gastro-resistant Tablets - Summary of Product Characteristics (SmPC). (emc). 2022-01-10 [2022-07-03]. （原始内容存档于2022-02-24）.

[Noxafil_FDA_label-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 Noxafil- posaconazole suspension Noxafil- posaconazole tablet, coated Noxafil- posaconazole solution. DailyMed. 2020-03-20 [2020-08-15]. （原始内容存档于2021-02-26）.

[Noxafil_EPAR-6] 6.0 ^6.1 Noxafil EPAR. European Medicines Agency. 2007-03-28 [2022-07-03]. （原始内容存档于2021-10-19）.

[pmid18035188-7] Schiller DS, Fung HB. Posaconazole: an extended-spectrum triazole antifungal agent. Clinical Therapeutics. September 2007, 29 (9): 1862–86. PMID 18035188. doi:10.1016/j.clinthera.2007.09.015.

[pmid18713852-8] Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH. Posaconazole: an oral triazole with an extended spectrum of activity. The Annals of Pharmacotherapy. October 2008, 42 (10): 1429–38 [2008-12-11]. PMID 18713852. S2CID 21777822. doi:10.1345/aph.1L005. ^{[失效連結]}

[9] Drug Approval Package: Noxafil (Posaconazole) NDA #022003. U.S. Food and Drug Administration (FDA). 2006-11-09 [2020-08-15]. （原始内容存档于2021-04-03）.

[10] Posaconazole: FDA-Approved Drugs. U.S. Food and Drug Administration (FDA). [2020-08-15]. （原始内容存档于2020-10-20）.

[11] First Generic Drug Approvals. U.S. Food and Drug Administration. 2022-10-17 [2022-11-28]. （原始内容存档于2021-01-26）.

[pmid14657086-12] Li X, Brown N, Chau AS, López-Ribot JL, Ruesga MT, Quindos G, et al. Changes in susceptibility to posaconazole in clinical isolates of Candida albicans. The Journal of Antimicrobial Chemotherapy. January 2004, 53 (1): 74–80. PMID 14657086. doi:10.1093/jac/dkh027 .

[pmid17143808-13] Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clinical Infectious Diseases. January 2007, 44 (1): 2–12. JSTOR 4485188. PMID 17143808. doi:10.1086/508774 .

[14] Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, Kontoyiannis DP. Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clinical Infectious Diseases. May 2006, 42 (10): 1398–403. PMID 16619151. doi:10.1086/503425 .

[ColonRice2019-15] Colon BL, Rice CA, Guy RK, Kyle DE. Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis. The Journal of Infectious Diseases. March 2019, 219 (7): 1095–1103. PMC 6420171 . PMID 30358879. doi:10.1093/infdis/jiy622.

[Goodman_&_Gilman-16] 16.0 ^16.1 Brunton L, Lazo J, Parker K. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. San Francisco: McGraw-Hill; 2006. ISBN 978-0-07-142280-2

[ClinicalPharm-17] Clinical Pharmacology Posaconazole. [2010-02-18]. （原始内容存档于2021-08-30）.

[Ashley_2017-18] 18.0 ^18.1 Ashley ED, Perfect JR. Pharmacology of azoles. Kauffman CA (编). UpToDate. Waltham, MA: UpToDate. October 2017 [2010-02-18]. （原始内容存档于2013-02-09）.

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