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 prevents vulnerable cells from dying by reversing the deregulation of BIRC3 brought on by B19V, interfering with the apoptotic process[2].

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Telbivudine (Epavudine) potently inhibited HBV DNA replication in HepG2.2.15 cells, reducing viral load by 90% at 0.5 μM [1]
Telbivudine (Epavudine) reduced parvovirus B19-induced apoptosis in CACs, decreasing the apoptotic rate from 45% (infected control) to 18% at 2 μM [2]
Telbivudine (Epavudine) downregulated the expression of cleaved caspase-3 and cleaved PARP (apoptosis-related proteins) in B19V-infected CACs, as detected by western blot [2]
Telbivudine (Epavudine) upregulated Bcl-2 (anti-apoptotic protein) mRNA expression by 2.3-fold and downregulated Bax (pro-apoptotic protein) mRNA expression by 0.4-fold in B19V-infected CACs (PCR analysis) [2]
Telbivudine (Epavudine) showed low cytotoxicity in HepG2.2.15 cells and CACs, with CC50 values > 20 μM [1][2]
Telbivudine (Epavudine) inhibited HBV surface antigen (HBsAg) secretion in HepG2.2.15 cells by 65% at 1 μM [1]

Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo (Europe) and Tyzeka (United States). Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance. Telbivudine is a synthetic thymidine nucleoside analogue, it is the L-isomer of thymidine. It is taken once daily. Telbivudine is a potent antiviral that provides effective and sustained viral suppression in patients with compensated CHB. In clinical trials, treatment outcomes were improved significantly more with telbivudine 600 mg once daily than with lamivudine 100 mg or adefovir 10 mg once daily, and telbivudine-treated patients had significantly less viral resistance than lamivudine-treated patients. Telbivudine is associated with a medium genetic barrier to resistance and, as patients with undetectable HBV DNA levels have significantly improved outcomes, it is recommended that HBV DNA levels are monitored at week 24 (and 6 monthly thereafter), with the addition of a nucleoside/nucleotide analogue without cross resistance (such as adefovir dipivoxil) if viraemia is present to reduce the risk of resistance (Roadmap concept). Telbivudine was generally well tolerated in clinical trials for periods of up to 4 years, and has a similar tolerability profile to that of lamivudine.

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Telbivudine (Epavudine) reduced serum HBV DNA levels by 2.1 log10 copies/mL in HBV-transgenic mice after oral administration of 30 mg/kg/day for 4 weeks [1]
Telbivudine (Epavudine) improved liver function in HBV-transgenic mice, decreasing serum alanine aminotransferase (ALT) levels from 180 U/L (control) to 85 U/L [1]
Telbivudine (Epavudine) reduced hepatic HBV core antigen (HBcAg) expression by 70% in HBV-transgenic mice, as detected by immunohistochemistry [1]

HBV reverse transcriptase inhibition assay: Prepare a reaction mixture containing recombinant HBV reverse transcriptase, poly(rA)-oligo(dT) template-primer, and [3H]-dTTP. Incubate with serial dilutions of Telbivudine (Epavudine) at 37°C for 120 min. Terminate the reaction with trichloroacetic acid, filter through glass fiber filters, and measure radioactivity to calculate the inhibition rate of HBV reverse transcriptase [1]

HBV antiviral cell assay: Seed HepG2.2.15 cells in 96-well plates at 3×104 cells/well and incubate for 24 h. Treat with Telbivudine (Epavudine) at concentrations ranging from 0.01 to 20 μM for 72 h. Collect cell culture supernatant to detect HBV DNA levels by real-time PCR and HBsAg by ELISA; calculate EC50 and CC50 (via MTT assay) [1]
Parvovirus B19-induced apoptosis cell assay: Isolate CACs from human peripheral blood and culture in 6-well plates at 1×106 cells/well. Infect with B19V (MOI = 10) for 2 h, then add Telbivudine (Epavudine) (0.5–5 μM) and incubate for 72 h. Collect cells to detect apoptotic rate by Annexin V-FITC/PI flow cytometry; extract proteins for western blot analysis of caspase-3, PARP, Bcl-2, and Bax; extract RNA for RT-PCR to quantify Bcl-2 and Bax mRNA levels [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
Telbivudine is absorbed after oral administration. A single dose of 600 mg telbivudine, taken concurrently with a high-fat (approximately 55 g) and high-calorie (approximately 950 kcal) meal, has no effect on the absorption or exposure of telbivudine. Telbivudine is primarily excreted unchanged in the urine.
7.6 ± 2.9 L/h [Normal renal function (Clcr > 80 mL/min)]
5.0 ± 1.2 L/h [Mild renal impairment (Clcr = 50-80 mL/min)]
2.6 ± 1.2 L/h [Moderate renal impairment (Clcr = 30-49 mL/min)]
0.7 ± 0.4 L/h [Severe renal impairment (Clcr < 30 mL/min)]

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Metabolism/Metabolites
None. Metabolites of telbivudine were detected in humans after administration of [14C]-telbivudine. Telbivudine is neither a substrate nor an inhibitor of the cytochrome P450 (CYP450) enzyme system.

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Biological half-life
Approximately 15 hours. The oral bioavailability of telbivudine (epavudine) in humans is 88%[1]. Telbivudine (epavudine) is rapidly absorbed in the human body. After oral administration of 600 mg, the peak plasma concentration (Cmax) is 3.6 μg/mL, and the time to peak concentration (Tmax) is 1-1.5 hours[1]. After taking 600 mg of telbivudine (epavudine) once daily, the area under the plasma concentration-time curve (AUC0-24h) in humans is 26.1 μg·h/mL[1].
The volume of distribution (Vd) of telbivudine in the human body is 1.2 L/kg [1]
The plasma elimination half-life (t1/2) of telbivudine in the human body is 15 hours [1]
Renal excretion is the main elimination route, with 70-80% of the administered dose excreted unchanged in the urine [1]
The plasma protein binding rate of telbivudine in the human body is low (<3%) [1]

Hepatotoxicity
Telbivudine shares many similarities with other L-nucleoside analogs (lamivudine, emtricitabine) and is associated with transient exacerbations of hepatitis B during and after treatment for chronic hepatitis B. In patients receiving telbivudine, 5% to 10% experience serum ALT elevations exceeding three times the normal value, comparable to other nucleoside analogs. Nucleoside analog treatment can result in three types of exacerbations: transient exacerbations that are usually asymptomatic before and after the initial treatment phase (treatment-phase exacerbation), disease exacerbations following antiviral resistance to telbivudine (breakthrough exacerbation), and disease exacerbations following discontinuation of the drug (discontinuation-phase exacerbation). Cases of hepatitis B exacerbation following antiviral resistance or discontinuation of telbivudine can be severe, with some cases even progressing to acute liver failure. No cases of lactic acidosis with hepatic steatosis have been reported with telbivudine treatment for hepatitis B, but there have been sporadic reports of suspected mitochondrial damage with myopathy. Clinical trials of telbivudine treatment in pregnant women who were positive for serum HBsAg and HBeAg and had high HBV DNA levels showed that the therapy appeared to reduce or even eliminate mother-to-child transmission. However, some pregnant women with active hepatitis B and elevated ALT levels before treatment experienced hepatitis B relapse after discontinuation of the drug. For women with "immune-tolerant" hepatitis B who had high HBV DNA levels but no elevated serum transaminases, relapse after discontinuation of the drug was uncommon; HBV DNA levels returned to previous levels after discontinuation, but relapse did not occur. Probability score: E (unlikely to cause clinically significant liver damage). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Telbivudine has been withdrawn from the US market. No studies have been conducted in breastfeeding women receiving treatment for hepatitis B infection. Alternative treatments are recommended, especially during the breastfeeding of newborns or premature infants.
As long as infants receive hepatitis B immunoglobulin and hepatitis B vaccine at birth, there is no difference in infection rate between breastfed and formula-fed infants born to mothers with hepatitis B infection. Mothers with hepatitis B are encouraged to breastfeed their infants after these preventive measures are taken.
◉ Effects on breastfed infants
No relevant published information was found as of the revision date.
◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date.

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Protein binding
Telbivudine has a low in vitro binding rate to human plasma proteins (3.3%).

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Telbivudine (epavudine) In HBV transgenic mice, doses up to 100 mg/kg/day for 12 weeks did not show significant hepatotoxicity [1].
In humans, the most common adverse reactions to telbivudine (epavudine) (600 mg/day) were fatigue (12%), headache (10%), and nausea (8%), with no other adverse reactions. Reported toxicities were grade 3-4 [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, therefore drug interactions are minimal [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'-deoxynucleoside, the L-enantiomer of thymine. It is a synthetic thymidine nucleoside analog with activity against hepatitis B virus DNA polymerase. It is an antiviral drug and also an EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor. Functionally related to thymine, it is an enantiomer of thymidine. Telbivudine is a synthetic thymidine nucleoside analog with specific activity against hepatitis B virus. It is well-tolerated orally, non-toxic, and has no dose-limiting side effects. Telbivudine is a hepatitis B virus nucleoside analog reverse transcriptase inhibitor. Its mechanism of action is as a nucleoside reverse transcriptase inhibitor. Telbivudine is a nucleoside analog and an antiviral drug that inhibits the replication of hepatitis B virus (HBV) and can be used alone or in combination with other drugs to treat hepatitis B. Telbivudine does not appear to be a primary cause of drug-induced liver injury, but it may cause relapse of primary hepatitis B during treatment or after discontinuation. Telbivudine is a synthetic thymidine nucleoside analog with highly specific antiviral activity and is used to treat hepatitis B virus (HBV). Intracellularly, telbivudine is phosphorylated to its active metabolite, telbivudine triphosphate. Dideoxytelbivudine triphosphate competes with thymidine for incorporation into viral DNA, leading to DNA chain termination and inhibition of HBV DNA polymerase (reverse transcriptase). This results in the inhibition of HBV DNA replication and viral transmission. A thymidine derivative and antiviral drug that inhibits HBV DNA synthesis and is used to treat chronic hepatitis B. See also: thymidine (note moved to).

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Drug Indications
For the treatment of adults and adolescents aged ≥16 years with chronic hepatitis B who have evidence of viral replication and persistently elevated serum transaminases (ALT or AST) or evidence of histologically active disease.

Sebivo is indicated for the treatment of adults with chronic hepatitis B and compensated liver disease who have evidence of viral replication, persistently elevated serum alanine aminotransferase (ALT) levels, and evidence of histologically active inflammation and/or fibrosis.
Sebivo should only be considered when alternative antiviral drugs with a higher genetic barrier to resistance are unavailable or unsuitable.

Treatment of Chronic Hepatitis B

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

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Pharmacodynamics
Telbivudine is a synthetic thymidine nucleoside analog with anti-hepatitis B virus (HBV) activity. Telbivudine is the unmodified β-L enantiomer of the naturally occurring nucleoside thymidine. It is phosphorylated by interaction with cellular kinases to form the active metabolite telbivudine 5'-triphosphate.

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Telbivudine (epavudine) is a synthetic thymidine nucleoside analog used to treat chronic hepatitis B virus infection [1].
Telbivudine (epavudine) exerts its anti-HBV effect by being converted into telbivudine triphosphate in cells, which competes with thymidine triphosphate for incorporation into HBV DNA, thereby terminating viral DNA synthesis [1].
Telbivudine (epavudine) is indicated for the treatment of adult patients with chronic hepatitis B who have evidence of viral replication and liver inflammation [1].
Telbivudine (epavudine) protects against parvovirus B19-induced damage by regulating circulating angiogenesis. Bcl-2/Bax apoptosis 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

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)

Solubility in Formulation 1: ≥ 3.25 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 3.25 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 3.25 mg/mL (13.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10 mg/mL (41.28 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)