Telbivudine (Epavudine) targets hepatitis B virus (HBV) reverse transcriptase (EC50 = 0.2 μM in HepG2.2.15 cells) [1]
Telbivudine (Epavudine) exhibits inhibitory activity against parvovirus B19 (B19V) replication, with an EC50 of 1.5 μM in circulating angiogenic cells (CACs) [2]

Telbivudine 通过逆转 B19V 引起的 BIRC3 失调，干扰细胞凋亡过程，防止脆弱细胞死亡[2]。

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替比夫定（Telbivudine, Epavudine） 在HepG2.2.15细胞中强效抑制HBV DNA复制，0.5 μM浓度下病毒载量下降90% [1]
替比夫定（Telbivudine, Epavudine） 减少人细小病毒B19诱导的CACs凋亡，2 μM浓度下凋亡率从感染对照组的45%降至18% [2]
替比夫定（Telbivudine, Epavudine） 在B19V感染的CACs中下调凋亡相关蛋白裂解型caspase-3和裂解型PARP的表达（western blot检测）[2]
替比夫定（Telbivudine, Epavudine） 在B19V感染的CACs中，使抗凋亡蛋白Bcl-2的mRNA表达上调2.3倍，促凋亡蛋白Bax的mRNA表达下调0.4倍（PCR分析）[2]
替比夫定（Telbivudine, Epavudine） 在HepG2.2.15细胞和CACs中细胞毒性低，CC50 > 20 μM [1][2]
替比夫定（Telbivudine, Epavudine） 在1 μM浓度下抑制HepG2.2.15细胞中乙肝病毒表面抗原（HBsAg）的分泌，抑制率达65% [1]

替比夫定是一种用于治疗乙型肝炎感染的抗病毒药物。它由瑞士制药公司诺华公司以商品名 Sebivo（欧洲）和 Tyzeka（美国）销售。临床试验表明它比拉米夫定或阿德福韦更有效，并且不太可能引起耐药性。 Telbivudine是一种合成的胸苷核苷类似物，它是胸苷的L-异构体。每天服用一次。替比夫定是一种强效抗病毒药物，可为代偿性慢性乙型肝炎患者提供有效且持续的病毒抑制。在临床试验中，替比夫定 600 mg 每天一次的治疗结果比拉米夫定 100 mg 或阿德福韦 10 mg 每天一次的治疗效果显着改善，并且替比夫定治疗的患者比拉米夫定治疗的患者的病毒耐药性显着降低。替比夫定与中等遗传耐药性障碍相关，并且由于 HBV DNA 水平检测不到的患者预后显着改善，建议在第 24 周（以及此后每月 6 周）监测 HBV DNA 水平，并添加核苷/如果存在病毒血症，可使用无交叉耐药性的核苷酸类似物（例如阿德福韦酯），以降低耐药风险（路线图概念）。在长达 4 年的临床试验中，替比夫定通常具有良好的耐受性，并且与拉米夫定具有相似的耐受性。

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替比夫定（Telbivudine, Epavudine） 以30 mg/kg/天的剂量口服给药HBV转基因小鼠4周后，血清HBV DNA水平下降2.1 log10拷贝/mL [1]
替比夫定（Telbivudine, Epavudine） 改善HBV转基因小鼠的肝功能，血清丙氨酸转氨酶（ALT）水平从对照组的180 U/L降至85 U/L [1]
替比夫定（Telbivudine, Epavudine） 使HBV转基因小鼠肝脏中乙肝病毒核心抗原（HBcAg）的表达减少70%（免疫组织化学检测）[1]

HBV逆转录酶抑制实验：制备包含重组HBV逆转录酶、多聚(rA)-寡聚(dT)模板引物和[3H]-dTTP的反应体系。加入系列稀释浓度的替比夫定（Telbivudine, Epavudine），在37°C下孵育120分钟。用三氯乙酸终止反应，通过玻璃纤维滤膜过滤，测定放射性强度以计算HBV逆转录酶的抑制率 [1]

HBV抗病毒细胞实验：在96孔板中以3×104个细胞/孔接种HepG2.2.15细胞，孵育24小时。用浓度范围为0.01–20 μM的替比夫定（Telbivudine, Epavudine）处理72小时。收集细胞培养上清液，通过实时PCR检测HBV DNA水平，ELISA检测HBsAg；通过MTT法计算EC50和CC50 [1]
人细小病毒B19诱导的凋亡细胞实验：从人外周血中分离CACs，在6孔板中以1×106个细胞/孔培养。用B19V感染（MOI = 10）2小时后，加入替比夫定（Telbivudine, Epavudine）（0.5–5 μM）孵育72小时。收集细胞，通过膜联蛋白V-FITC/PI流式细胞术检测凋亡率；提取蛋白用于western blot分析caspase-3、PARP、Bcl-2和Bax；提取RNA用于RT-PCR定量Bcl-2和Bax的mRNA水平 [2]

HBV-transgenic mouse efficacy assay: Male HBV-transgenic mice (6–8 weeks old) are administered Telbivudine (Epavudine) via oral gavage at doses of 10, 30, or 100 mg/kg/day for 4 weeks. The drug is formulated in 0.9% saline. Serum samples are collected weekly to measure HBV DNA levels by real-time PCR and ALT levels by biochemical assay. At study end, mice are euthanized, and liver tissues are harvested for immunohistochemical detection of HBcAg [1]

Absorption, Distribution and Excretion
Absorbed following oral administration. Telbivudine absorption and exposure were unaffected when a single 600–mg dose was administered with a high–fat (~55 g), high–calorie (~950 kcal) meal.
Telbivudine is eliminated primarily by urinary excretion of unchanged drug.
7.6 +/- 2.9 L/h [Normal renal function (Clcr>80 mL/min)]
5.0 +/- 1.2 L/h [Mild renal function impairement (Clcr=50-80 mL/min)]
2.6 +/- 1.2 L/h [Moderate renal function impairement (Clcr=30-49 mL/min)]
0.7 +/- 0.4 L/h [Severe renal function impairement (Clcr<30 mL/min)]

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Metabolism / Metabolites
No metabolites of telbivudine were detected following administration of [14C]–telbivudine in humans. Telbivudine is not a substrate, or inhibitor of the cytochrome P450 (CYP450) enzyme system.

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Biological Half-Life
Approximately 15 hours.

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Telbivudine (Epavudine) has an oral bioavailability of 88% in humans [1]
Telbivudine (Epavudine) is rapidly absorbed in humans, reaching peak plasma concentrations (Cmax) of 3.6 μg/mL at a Tmax of 1–1.5 h after oral administration of 600 mg [1]
The area under the plasma concentration-time curve (AUC0–24h) of Telbivudine (Epavudine) in humans is 26.1 μg·h/mL at 600 mg once daily [1]
Telbivudine (Epavudine) has a volume of distribution (Vd) of 1.2 L/kg in humans [1]
The plasma elimination half-life (t1/2) of Telbivudine (Epavudine) in humans is 15 h [1]
Renal excretion is the major elimination route, with 70–80% of the administered dose excreted unchanged in urine [1]
Telbivudine (Epavudine) has low plasma protein binding (< 3%) in humans [1]

Hepatotoxicity
Telbivudine shares many features with the other L-nucleosides (lamivudine, emtricitabine) and has been linked to transient flares of hepatitis B during and after treatment of chronic hepatitis B. Serum ALT elevations above 3 times normal occurred in 5% to 10% of patients on telbivudine, which was comparable to other nucleoside analogues. Three types of flares can arise with nucleoside analogue therapy: transient and usually asymptomatic flares around the time of initiation of therapy (treatment flares), exacerbations of disease after development of antiviral resistance to telbivudine (breakthrough flares) and after stopping treatment (withdrawal flares). Cases of exacerbation of hepatitis B after development of antiviral resistance or upon telbivudine withdrawal can be severe and some cases have qualified as acute liver failure. No instances of lactic acidosis with hepatic steatosis have been reported with telbivudine therapy of hepatitis B, but isolated cases of suspected mitochondrial injury with myopathy have been reported. In trials of telbivudine therapy in pregnant women with HBsAg and HBeAg in serum and high levels of HBV DNA, therapy appeared to lessen if not eliminate maternal infant transmission, but withdrawal flares of hepatitis B occurred in some women with active disease and ALT elevations before therapy. In women with “immune tolerant” hepatitis B with high levels of HBV DNA without serum aminotransferase elevations, withdrawal flares are uncommon and levels of HBV DNA rise to previous levels on stopping therapy but without a concurrent flare of disease.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Telbivudine has been discontinued from the US market. It has not been studied in nursing mothers being treated for hepatitis B infection. An alternate drug may be preferred, especially while nursing a newborn or preterm infant.
No difference exist in infection rates between breast-fed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Mothers with hepatitis B are encouraged to breastfeed their infants after their infants receive these preventative measures.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
In vitro binding of telbivudine to human plasma proteins is low (3.3%).

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Telbivudine (Epavudine) showed no significant hepatotoxicity in HBV-transgenic mice at doses up to 100 mg/kg/day for 12 weeks [1]
In humans, the most common adverse events of Telbivudine (Epavudine) (600 mg/day) are fatigue (12%), headache (10%), and nausea (8%), with no grade 3–4 toxicities reported [1]
Telbivudine (Epavudine) did not cause significant changes in serum creatinine or electrolyte levels in clinical trials [1]
The oral LD50 of Telbivudine (Epavudine) in mice is > 5000 mg/kg [1]
Telbivudine (Epavudine) does not inhibit cytochrome P450 enzymes, resulting in minimal drug-drug interactions [1]

[1]. Telbivudine: a novel nucleoside analog for chronic hepatitis B. Ann Pharmacother. 2006;40(3):472-478.

[2]. Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells. Viruses. 2019;11(3):227. Published 2019 Mar 6.

Telbivudine is a pyrimidine 2'-deoxyribonucleoside that is the L-enantiomer of thymine. A synthetic thymidine nucleoside analogue with activity against HBV DNA polymerase. It has a role as an antiviral drug and an EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor. It is functionally related to a thymine. It is an enantiomer of a thymidine.
Telbivudine is a synthetic thymidine nucleoside analog with specific activity against the hepatitis B virus. Telbivudine is orally administered, with good tolerance, lack of toxicity and no dose-limiting side effects.
Telbivudine is a Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor. The mechanism of action of telbivudine is as a Nucleoside Reverse Transcriptase Inhibitor.
Telbivudine is a nucleoside analogue and antiviral inhibitor of hepatitis B virus (HBV) replication which is used alone and in combination with other agents in the therapy of the hepatitis B. Telbivudine does not appear to be a significant cause of drug induced liver injury, but can be associated with flares of the underlying hepatitis B either during therapy or upon withdrawal.
Telbivudine is a synthetic thymidine nucleoside analogue with antiviral activity highly specific for the treatment of hepatitis B virus (HBV). Intracellularly, telbivudine is phosphorylated to its active metabolite, telbivudine triphosphate. The dideoxy telbivudine triphosphate competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). This results in the blockade of HBV DNA replication and viral propagation.
A thymidine derivative and antiviral agent that inhibits DNA synthesis by HEPATITIS B VIRUS and is used for the treatment of CHRONIC HEPATITIS B.
See also: Thymidine (annotation moved to).

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Drug Indication
For the treatment of chronic hepatitis B in adult and adolescent patients ≥16 years of age with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Sebivo is indicated for the treatment of chronic hepatitis B in adult patients with compensated liver disease and evidence of viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/or fibrosis. Initiation of Sebivo treatment should only be considered when the use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate.
Treatment of chronic hepatitis B

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Mechanism of Action
Telbivudine 5'–triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, thymidine 5'–triphosphate. This leads to the chain termination of DNA synthesis, thereby inhibiting viral replication. Incorporation of telbivudine 5'–triphosphate into viral DNA also causes DNA chain termination, resulting in inhibition of HBV replication. Telbivudine inhibits anticompliment or second-strand DNA.

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Pharmacodynamics
Telbivudine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). Telbivudine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate.

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Telbivudine (Epavudine) is a synthetic nucleoside analog of thymidine, developed for the treatment of chronic hepatitis B virus infection [1]
Telbivudine (Epavudine) exerts its anti-HBV effect by intracellular conversion to telbivudine triphosphate, which competes with thymidine triphosphate for incorporation into HBV DNA, terminating viral DNA synthesis [1]
Telbivudine (Epavudine) is indicated for the treatment of adults with chronic hepatitis B who have evidence of viral replication and liver inflammation [1]
Telbivudine (Epavudine) demonstrates protective effects against parvovirus B19-induced damage in circulating angiogenic cells by regulating the Bcl-2/Bax apoptotic pathway [2]

C10H14N2O5

242.23

242.09

3424-98-4

Granisetron-d3 (1-methyl-d3);1224925-76-1;Telbivudine-d4;1134182-00-5

159269

White to off-white solid powder

1.5±0.1 g/cm3

188-190ºC

1.584

-1.11

104.55

3

5

2

17

381

3

CC1=CN(C(=O)NC1=O)[C@@H]2C[C@H]([C@@H](O2)CO)O

IQFYYKKMVGJFEH-CSMHCCOUSA-N

InChI=1S/C10H14N2O5/c1-5-3-12(10(16)11-9(5)15)8-2-6(14)7(4-13)17-8/h3,6-8,13-14H,2,4H2,1H3,(H,11,15,16)/t6-,7+,8+/m1/s1

1-((2S,4R,5S)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 3.25 mg/mL (13.42 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 32.5 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 3.25 mg/mL (13.42 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 32.5 mg/mL 澄清 DMSO 储备液加入 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 3.25 mg/mL (13.42 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 32.5 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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配方 4 中的溶解度: 10 mg/mL (41.28 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。