用户:Gavin730/他克莫司

Gavin730/他克莫司
临床资料
商品名（英语：Drug nomenclature）	Prograf, Advagraf, Protopic, others
其他名称	FK-506, fujimycin
AHFS/Drugs.com	Monograph
MedlinePlus	a601117
核准状况	欧 EMA: yes; 美 DailyMed: Tacrolimus;
怀孕分级	澳: C ; ;
给药途径	Topical, by mouth, intravenous (IV)
ATC码	D11AH01 (WHO) ; L04AD02;
法律规范状态
法律规范	美：处方药（℞-only）; 处方药（℞-only）;
药物动力学数据
生物利用度	24% (5–67%), less after eating food rich in fat
血浆蛋白结合率	≥98.8%
药物代谢	Hepatic CYP3A4, CYP3A5
生物半衰期	11.3 h for transplant patients (range 3.5–40.6 h)
排泄途径	Mostly faecal
识别信息
	IUPAC命名法 (−)-(3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,26aS)-8-allyl-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-{(E)-2-[(1R,3R,4R)-4-hydroxy-3-methylcyclohexyl]-1-methylvinyl}-14,16-dimethoxy-4,10,12,18-tetramethyl-15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosane-1,7,20,21(4H,23H)-tetrone; ;
CAS号	104987-11-3
PubChem CID	445643;
DrugBank	DB00864 ;
ChemSpider	393220 ;
UNII	Y5L2157C4J;
KEGG	D00107 ; C01375 ;
ChEBI	CHEBI:61049;
ChEMBL	ChEMBL269732 ;
PDB配体ID	FK5 (PDBe, RCSB PDB);
化学信息
化学式	C44H69NO12
摩尔质量	804.018
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C3C(=O)N1CCCC[C@H]1C(=O)O[C@H](C(=C/[C@@H]2CC[C@@H](O)[C@H](OC)C2)/C)[C@H](C)[C@@H](O)CC(=O)[C@@H](/C=C(/C[C@@H](C[C@H](OC)[C@H]4O[C@]3(O)[C@H](C)C[C@@H]4OC)C)C)C\C=C;
	InChI InChI=1S/C44H69NO12/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3/b25-19+,27-21+/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+/m0/s1 ; Key:QJJXYPPXXYFBGM-LFZNUXCKSA-N ;

他克莫司是一种免疫抑制剂。它被用于降低器官移植后的排斥风险, 也可以被用作外用药物来治疗T细胞介导免疫产生的疾病，例如异位性皮肤炎和牛皮藓. 它还可以用于治疗骨髓移植后的虹彩炎、微小病变的恶化、木村氏症、白癜风和猫狗的干眼症。^[2]^[3]

他克莫司可抑制钙调磷酸酶, 从而影响白细胞介素-2的产生。这种白细胞介素是获得性免疫系统中的一部分，可以促进T细胞的发育和增殖。

它是一种在1987年于一份来自日本的含有的土壤样本中被首次发现的大环内酯^[4]。

医疗用途

器官移植

他克莫司具有和环孢素相似的免疫抑制性，但效果远强于环孢素. 在一项研究中他克莫司与环孢素相比可以显著降低发生急性排斥反应的概率(30.7%vs46.4%)。^[5]在肝移植的第一年中他克莫司的疗效也优于环孢素。^[6]^[7]长期疗效则不及环孢素。他克莫司通常作为器官移植后药物的一种，另外还有皮质类固醇, 霉酚酸和如 [[en:basiliximab|巴利昔单抗]的白细胞介素-2受体抑制剂]. Dosages are titrated to target blood levels.

溃疡性结肠炎

近几年他克莫司已被用于抑制溃疡性结肠炎。尽管现在它几乎尽在试验中使用，但已经显示出很好的疗效。^[8]^[9]

皮炎

他克莫司可作为软膏来治疗皮肤炎特别是特异性皮炎, . 它以和类固醇相似的方式抑制炎症，效果和中效类固醇相似。他克莫司与类固醇相比具有不会引起萎缩和类固醇的其他副作用^[10]

狼疮性肾炎

与其他药物相比他克莫司可以降低狼疮性肾炎严重感染的风险。^[11]

^ ^1.0 ^1.1 Tacrolimus Use During Pregnancy. Drugs.com. 3 October 2019 [29 April 2020].
^ Berdoulay A, English RV, Nadelstein B. Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca. Veterinary Ophthalmology. 2005, 8 (4): 225–32. PMID 16008701. doi:10.1111/j.1463-5224.2005.00390.x.
^ Tacrolimus for Dogs and Cats.
^ Baldo A, Cafiero M, Di Caterino P, Di Costanzo L. Tacrolimus ointment in the management of atopic dermatitis. Clin Cosmet Investig Dermatol. January 2009, 2: 1–7. PMC 3047924 . PMID 21436963. doi:10.2147/ccid.s3378.
^ McCauley, Jerry. Long-Term Graft Survival In Kidney Transplant Recipients. Slide Set Series on Analyses of Immunosuppressive Therapies. Medscape. 2004-05-19 [2006-06-06].
^ Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. McAlister V , 编. Cyclosporin versus tacrolimus for liver transplanted patients. The Cochrane Database of Systematic Reviews. October 2006, 4 (4): CD005161. PMID 17054241. doi:10.1002/14651858.CD005161.pub2.
^ O'Grady JG, Burroughs A, Hardy P, Elbourne D, Truesdale A. Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial. Lancet. October 2002, 360 (9340): 1119–25. PMID 12387959. doi:10.1016/S0140-6736(02)11196-2.
^ Baumgart DC, Pintoffl JP, Sturm A, Wiedenmann B, Dignass AU. Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease--a long-term follow-up. The American Journal of Gastroenterology. May 2006, 101 (5): 1048–56. PMID 16573777.
^ Baumgart DC, Macdonald JK, Feagan B. Baumgart DC , 编. Tacrolimus (FK506) for induction of remission in refractory ulcerative colitis. The Cochrane Database of Systematic Reviews. July 2008, 16 (3): CD007216. PMID 18646177. doi:10.1002/14651858.CD007216.
^ 引用错误：没有为名为AC-Protopic的参考文献提供内容
^ Singh JA, Hossain A, Kotb A, Wells G. Risk of serious infections with immunosuppressive drugs and glucocorticoids for lupus nephritis: a systematic review and network meta-analysis. BMC Medicine. September 2016, 14 (1): 137. PMC 5022202 . PMID 27623861. doi:10.1186/s12916-016-0673-8.

[Drugs.com_pregnancy-1] 1.0 ^1.1 Tacrolimus Use During Pregnancy. Drugs.com. 3 October 2019 [29 April 2020].

[2] Berdoulay A, English RV, Nadelstein B. Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca. Veterinary Ophthalmology. 2005, 8 (4): 225–32. PMID 16008701. doi:10.1111/j.1463-5224.2005.00390.x.

[3] Tacrolimus for Dogs and Cats.

[4] Baldo A, Cafiero M, Di Caterino P, Di Costanzo L. Tacrolimus ointment in the management of atopic dermatitis. Clin Cosmet Investig Dermatol. January 2009, 2: 1–7. PMC 3047924 . PMID 21436963. doi:10.2147/ccid.s3378.

[Medscape2004-McCauley-5] McCauley, Jerry. Long-Term Graft Survival In Kidney Transplant Recipients. Slide Set Series on Analyses of Immunosuppressive Therapies. Medscape. 2004-05-19 [2006-06-06].

[6] Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. McAlister V , 编. Cyclosporin versus tacrolimus for liver transplanted patients. The Cochrane Database of Systematic Reviews. October 2006, 4 (4): CD005161. PMID 17054241. doi:10.1002/14651858.CD005161.pub2.

[7] O'Grady JG, Burroughs A, Hardy P, Elbourne D, Truesdale A. Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial. Lancet. October 2002, 360 (9340): 1119–25. PMID 12387959. doi:10.1016/S0140-6736(02)11196-2.

[8] Baumgart DC, Pintoffl JP, Sturm A, Wiedenmann B, Dignass AU. Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease--a long-term follow-up. The American Journal of Gastroenterology. May 2006, 101 (5): 1048–56. PMID 16573777.

[9] Baumgart DC, Macdonald JK, Feagan B. Baumgart DC , 编. Tacrolimus (FK506) for induction of remission in refractory ulcerative colitis. The Cochrane Database of Systematic Reviews. July 2008, 16 (3): CD007216. PMID 18646177. doi:10.1002/14651858.CD007216.

[AC-Protopic-10] 引用错误：没有为名为AC-Protopic的参考文献提供内容

[11] Singh JA, Hossain A, Kotb A, Wells G. Risk of serious infections with immunosuppressive drugs and glucocorticoids for lupus nephritis: a systematic review and network meta-analysis. BMC Medicine. September 2016, 14 (1): 137. PMC 5022202 . PMID 27623861. doi:10.1186/s12916-016-0673-8.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]