福沙那韦

福沙那韦
临床资料
商品名（英语：Drug nomenclature）	Lexiva, Telzir
其他名称	Fosamprenavir calcium (USAN US)
AHFS/Drugs.com	Monograph
MedlinePlus	a604012
核准状况	欧 EMA: yes;
怀孕分级	澳: B3 ; ;
给药途径	By mouth
ATC码	J05AE07 (WHO) ;
法律规范状态
法律规范	加：处方药（℞-only）; 欧：Rx-only; 英：处方药（℞-only） (POM); 美：处方药（℞-only）;
药物动力学数据
生物利用度	Unknown
血浆蛋白结合率	90%
药物代谢	Hydrolysed to amprenavir and phosphate in GI tract epithelium
生物半衰期	7.7 hours
排泄途径	Fecal (as metabolites of amprenavir)
识别信息
	IUPAC命名法 {[(2R,3S)-1-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxy}phosphonic acid; ;
CAS号	226700-79-4 ; 226700-81-8
PubChem CID	131536; as salt: 131535;
DrugBank	DB01319 ; as salt: DBSALT001228;
ChemSpider	116245 ; as salt: 116244;
UNII	WOU1621EEG; as salt: ID1GU2627N ;
KEGG	D02497 ; as salt: D03835;
ChEBI	CHEBI:82941;
ChEMBL	ChEMBL1664 ; as salt: ChEMBL1200734;
NIAID ChemDB	082186;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID2048296 ;
化学信息
化学式	C25H36N3O9PS
摩尔质量	585.61 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C(O[C@H]1CCOC1)N[C@@H](Cc2ccccc2)[C@H](OP(=O)(O)O)CN(CC(C)C)S(=O)(=O)c3ccc(N)cc3;
	InChI InChI=1S/C25H36N3O9PS/c1-18(2)15-28(39(33,34)22-10-8-20(26)9-11-22)16-24(37-38(30,31)32)23(14-19-6-4-3-5-7-19)27-25(29)36-21-12-13-35-17-21/h3-11,18,21,23-24H,12-17,26H2,1-2H3,(H,27,29)(H2,30,31,32)/t21-,23-,24+/m0/s1 ; Key:MLBVMOWEQCZNCC-OEMFJLHTSA-N ; ; as salt: InChI=1S/C25H36N3O9PS.Ca/c1-18(2)15-28(39(33,34)22-10-8-20(26)9-11-22)16-24(37-38(30,31)32)23(14-19-6-4-3-5-7-19)27-25(29)36-21-12-13-35-17-21;/h3-11,18,21,23-24H,12-17,26H2,1-2H3,(H,27,29)(H2,30,31,32);/q;+2/p-2/t21-,23-,24+;/m0./s1; Key:PMDQGYMGQKTCSX-HQROKSDRSA-L;

福沙那韦（英语：Fosamprenavir），商品名Lexiva和Telzir，是一种用于治疗HIV/AIDS的药物。^[3]^[4]它是蛋白酶抑制剂和抗逆转录病毒药物安普那韦的前药。^[5]它由ViiV医疗保健公司作为钙盐销售。^[3]^[4]

福沙那韦于2003年10月在美国被批准用于医疗用途，^[6]并于2004年7月在欧盟获得批准。^[4]人体代谢福沙那韦以形成作为活性成分的安普那韦。^[3]

一项与洛匹那韦的头对头研究表明，这两种药物具有相当的效力，但服用福沙那韦的患者往往具有更高的血清胆固醇。^[7]

医疗用途

福沙那韦用于治疗HIV-1感染，通常但不一定与低剂量利托那韦或其他抗病毒药物联合使用。^[8]^[9]

副作用

最常见的不良反应是腹泻。其他常见的副作用包括头痛、头晕和皮疹，这通常是短暂的。严重的过敏反应（史蒂文斯-约翰逊综合征）很少见。^[8]

相互作用

安普那韦（福沙那韦的活性代谢物，存在于血浆、肝脏和其他器官中）通过肝酶CYP3A4代谢，并且对这种酶有微弱的抑制作用。这意味着与也被CYP3A4代谢的药物联合使用可以增加其血浆浓度，从而增加副作用；并与抑制CYP3A4的药物合用可增加安普那韦的浓度。^[8]

当将福沙那韦与低剂量的CYP3A4抑制剂利托那韦联合使用时，这种相互作用是有意的，因为它允许应用较低剂量的福沙那韦。^[8]

药理学

福沙那韦甚至在到达循环系统之前就被迅速激活为安普那韦。安普那韦是一种 HIV 蛋白酶抑制剂。^[8]

HIV-1蛋白酶二聚体与安普那韦（棒）结合在活性位点。PDB条目3nu3^[10]

参考文献

^ Telzir Product information. Health Canada. 25 April 2012 [2 October 2022]. （原始内容存档于14 June 2021）.
^ Telzir 700 mg film-coated tablets - Summary of Product Characteristics (SmPC). (emc). 22 June 2021 [2 October 2022]. （原始内容存档于6 December 2021）.
^ ^3.0 ^3.1 ^3.2 ^3.3 Lexiva- fosamprenavir calcium tablet, film coated Lexiva- fosamprenavir calcium suspension. DailyMed. 1 October 2020 [2 October 2022]. （原始内容存档于29 January 2022）.
^ ^4.0 ^4.1 ^4.2 ^4.3 Telzir EPAR. European Medicines Agency. 17 September 2018 [2 October 2022]. （原始内容存档于15 May 2021）.
^ Archived copy. [2022-10-03]. （原始内容存档于2021-06-28）.
^ Drug Approval Package: Lexiva (Fosamprenavir Calcium) NDA #021548. U.S. Food and Drug Administration (FDA). [2 October 2022]. （原始内容存档于15 April 2021）.
^ Eron J, Yeni P, Gathe J, Estrada V, DeJesus E, Staszewski S, et al. The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial. Lancet. August 2006, 368 (9534): 476–82. PMID 16890834. S2CID 33612672. doi:10.1016/S0140-6736(06)69155-1.
^ ^8.0 ^8.1 ^8.2 ^8.3 ^8.4 Jasek W (编). Austria-Codex 62nd. Vienna: Österreichischer Apothekerverlag. 2007: 8009–17. ISBN 978-3-85200-181-4 （German）.
^ Lexiva. Drugs.com (报告). Monograph.
^ Shen CH, Wang YF, Kovalevsky AY, Harrison RW, Weber IT. Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. The FEBS Journal. September 2010, 277 (18): 3699–714. PMC 2975871  . PMID 20695887. doi:10.1111/j.1742-4658.2010.07771.x.

外部链接

Fosamprenavir. Drug Information Portal. U.S. National Library of Medicine. [2022-11-02]. （原始内容存档于2021-02-25）.
Fosamprenavir calcium. Drug Information Portal. U.S. National Library of Medicine. [2022-11-02]. （原始内容存档于2022-10-02）.

[1] Telzir Product information. Health Canada. 25 April 2012 [2 October 2022]. （原始内容存档于14 June 2021）.

[2] Telzir 700 mg film-coated tablets - Summary of Product Characteristics (SmPC). (emc). 22 June 2021 [2 October 2022]. （原始内容存档于6 December 2021）.

[Lexiva_FDA_label-3] 3.0 ^3.1 ^3.2 ^3.3 Lexiva- fosamprenavir calcium tablet, film coated Lexiva- fosamprenavir calcium suspension. DailyMed. 1 October 2020 [2 October 2022]. （原始内容存档于29 January 2022）.

[Telzir_EPAR-4] 4.0 ^4.1 ^4.2 ^4.3 Telzir EPAR. European Medicines Agency. 17 September 2018 [2 October 2022]. （原始内容存档于15 May 2021）.

[5] Archived copy. [2022-10-03]. （原始内容存档于2021-06-28）.

[6] Drug Approval Package: Lexiva (Fosamprenavir Calcium) NDA #021548. U.S. Food and Drug Administration (FDA). [2 October 2022]. （原始内容存档于15 April 2021）.

[7] Eron J, Yeni P, Gathe J, Estrada V, DeJesus E, Staszewski S, et al. The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial. Lancet. August 2006, 368 (9534): 476–82. PMID 16890834. S2CID 33612672. doi:10.1016/S0140-6736(06)69155-1.

[Austria-Codex-8] 8.0 ^8.1 ^8.2 ^8.3 ^8.4 Jasek W (编). Austria-Codex 62nd. Vienna: Österreichischer Apothekerverlag. 2007: 8009–17. ISBN 978-3-85200-181-4 （German）.

[9] Lexiva. Drugs.com (报告). Monograph.

[10] Shen CH, Wang YF, Kovalevsky AY, Harrison RW, Weber IT. Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. The FEBS Journal. September 2010, 277 (18): 3699–714. PMC 2975871  . PMID 20695887. doi:10.1111/j.1742-4658.2010.07771.x.

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