印度索非布韦

【印度索非布韦说明书，怎么吃？】

索非布韦（印度）又名索磷布韦 索华迪 Sofosbuvir，索非布韦适用于处方药。索华迪可作为联合抗病毒治疗方案的组成部分，用于治疗成年人慢性HCV感染： (1)无肝硬化或患代偿期肝硬化（肝硬化早期）的基因1或4型慢性HCV成年人患者，可采用聚乙二醇干扰素/利巴韦林与索华迪联合治疗方案； (2)无肝硬化的治疗，索非布韦用法及注意事项,:【给药方法】 口服，随食物一起服用 【参考用法】 成年人。1片，一天一次。连续12周。必要时24周。 【注意事项】 与胺碘酮共同给药时发生严重症状性心动过缓。建议胺碘酮不与吉二代共同给药...

【作用机制】

主要成分索磷布韦（索非布韦）是NS5B聚合酶抑制剂，是一种丙型肝炎病毒（HCV）聚合酶抑制剂，作用于病毒RNA复制的核苷酸类似物NS5B聚合酶位点，能中止病毒复制。索磷布韦与聚乙二醇干扰素(pegylated interferon)/利巴韦林(ribavirin)或单独与利巴韦林联用，与标准治疗方案相比，治愈率更高且给药时间缩短。
 

【副作用】   

国外临床研究主要对索华迪与利巴韦林的合用进行了研究。在此情况下，未发现特定发生于索磷布韦的药品不良反应。在接受索华迪+利巴韦林或索华迪+利巴韦林+聚乙二醇干扰素α治疗的受试者中，最常发生的药品不良反应为疲劳、头痛、恶心与失眠。在中国的试验中，安全性特征与国外基本相似。


【给药方法】

 口服，随食物一起服用

【参考用法】

成年人。推荐剂量为每日一次，每次口服一片400mg片剂，随食物服用。


【注意事项】

合用会减少索华迪的血药浓度，降低疗效。抗癫痫药：卡马西平、苯妥英钠、磷苯妥英钠、苯巴比妥、奥卡西平；抗结核药：利福布丁、利福平、利福喷丁；抗艾滋病毒的蛋白酶抑制药：替拉那韦、利托那韦；某些草药：贯叶连翘。建议：服用DAAs治疗期间，不要使用中药保肝药。

某些药物合用会增加索华迪的血药浓度，引发不良反应。胺碘酮：美国FDA发出警告，索华迪与胺碘酮可能有相互作用，导致索华迪的血药浓度增加，引起心脏毒性。包括Harvoni、Epclusa、含SOF的联合方案。Eliglustat(高雪氏病)：可能增加索华迪的药物浓度，但具体后果不清，如同时使用随时监测索华迪的血药浓度。

联合达卡他韦(Daclatasvir)时请注意：口服避孕药、依非韦伦、阿扎那韦/利托那韦、奥美拉唑会与达卡他韦发生反应，应询问医生。

联合质子泵抑制剂（PPI）时请注意：治疗期间同时服用PPI可能导致持续病毒学应答（SVR）降低。



USES OF SOFOVIR TABLET

Chronic hepatitis C virus (HCV) infection

SOFOVIR TABLET SIDE EFFECTS
Common
Fatigue
Nausea
Headache
Insomnia (difficulty in sleeping)
Anemia (low number of red blood cells)

HOW TO USE SOFOVIR TABLET
Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Sofovir 400 mg Tablet is to be taken with food.

HOW SOFOVIR TABLET WORKS
Sofovir 400 mg Tablet is an antiviral medication. It works by lowering a load of hepatitis C virus in the body and removing the virus from the blood over a period of time.

SOFOVIR TABLET RELATED WARNINGS

warnings
Alcohol
Interaction with alcohol is unknown. Please consult your doctor.

warnings
Pregnancy

PROBABLY SAFE
Sofovir 400 mg Tablet is probably safe to use during pregnancy.
Animal studies have shown low or no adverse effect on the fetus, however, there are limited human studies. Please consult your doctor.

warnings
Lactation
Sofovir 400 mg Tablet is probably safe to use during lactation. Limited human data suggests that the drug does not represent a significant risk to the baby.

warnings
Driving
Do not drive unless you are feeling well.
Sofovir 400 mg Tablet, when taken together with other medicines for the treatment of hepatitis c infection, may produce dizziness, blurred vision and this may affect your ability to drive.

warnings
Kidney
Sofovir 400 mg Tablet should be used with caution in patients with severe kidney disease. Dose adjustment of Sofovir 400 mg Tablet may be needed. Please consult your doctor.
Limited information is available on use of Sofovir 400 mg Tablet in these patients. No dose adjustment is recommended in patients with mild to moderate kidney disease.

warnings
Liver
SAFE
Sofovir 400 mg Tablet is safe to use in patients with liver disease. No dose adjustment of Sofovir 400 mg Tablet is recommended.
WHAT IF YOU MISS A DOSE OF SOFOVIR TABLET?
If you miss a dose of Sofovir 400 mg Tablet, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Sofosbuvir

生物活性

产品描述	Sofosbuvir is a uridine monophosphate analog inhibitor of hepatitis C virus (HCV) polymerase NS5B that is used as an antiviral agent in the treatment of chronic hepatitis C.
靶点活性	HCV,EC50:92±5nM
体外活性	As HCV NS5B polymerase inhibitor, PSI-7977 displays more potent inhibitory activity against HCV RNA replication than PSI-7976 with EC50 of 92 nM versus 1.07 μM and EC90 of 0.29 μM versus 2.99 μM, consistent with that incubating clone A cells with PSI-7977 leads to a higher concentration of PSI-7409 than clone A cells incubated with PSI-7976. PSI-7977 is an effective substrate for CatA to form PSI-352707 with 18-30 fold more potency as compared with PSI-7976. Unlike GS-7976, however, the CES1-mediated hydrolysis of PSI-7977 does not progress in a time-dependent manner. [1] The S282T NS5B polymerase mutation but not S96T mutation confers resistance to PSI-7977 with EC90 increases from 0.42 μM to 7.8 μM. When assessed in an 8-day cytotoxicity assay, PSI-7977 displays no cytotoxicity against Huh7, HepG2, BxPC3, and CEM cells even at concentrations up to 100 μM. PSI-7977 treatment for 14 days shows a IC90 of 72.1 μM and 68.6 μM for the inhibition of mtDNA and rDNA, respectively, in HepG2 cells. [2] PSI-7977 exhibits potent activity against genotype (GT) 1a, 1b, and 2a (strain JFH-1) replicons and chimeric replicons containing GT 2a (strain J6), 2b, and 3a NS5B polymerase. Sequence analysis of the JFH-1 NS5B region indicates that additional amino acid changes including T179A, M289L, I293L, M434T, and H479P are selected both prior to and after the emergence of S282T, which are required to confer resistance to PSI-7977. [3]
体内活性
细胞实验	Cells are exposed to various concentrations of PSI-7977 for 8 days. At the end of the growth period, MTS dye from the CellTiter 96 AQueous One Solution Cell Proliferation Assay kit is added to each well, and the plate is incubated for an additional 2 hours. The absorbance at 490 nm is read with a Victor3 plate reader using themedium only controlwells as blanks. The 50% inhibition value (IC50) is determined by comparing the absorbance in wells containing cells and PSI-7977 to untreated cell control wells.(Only for Reference) 细胞系： Huh7, HepG2, BxPC3, and CEM

化学信息

分子量	529.45
分子式	C22H29FN3O9P
CAS	1190307-88-0
溶解度	DMSO: 93 mg/mL (175.7 mM) Ethanol: 93 mg/mL (175.7 mM) Water: 9 mg/mL (17 mM) （ < 1 mg/ml refers to the product slightly soluble or insoluble )
储存条件	store at -80°C
备注	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

配制溶液

	1 mg	5 mg	10 mg
1 mM	1.889 ml	9.444 ml	18.888 ml
5 mM	0.378 ml	1.889 ml	3.778 ml
10 mM	0.189 ml	0.944 ml	1.889 ml
50 mM	0.038 ml	0.189 ml	0.378 ml

参考文献
 
1. Murakami E, et al. J Biol Chem, 2010, 285(45), 34337-34347.
2. Sofia MJ, et al. J Med Chem, 2010, 53(19), 7202-7218.
3. Lam AM, et al. Antimicrob Agents Chemother, 2012, 56(6), 3359-3368.