Telbivudine

Identification

Name
Telbivudine
Accession Number
DB01265
Description

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 242.2286
Monoisotopic: 242.090271568
Chemical Formula
C10H14N2O5
Synonyms
  • 1-(2-deoxy-β-L-ribofuranosyl)-5-methyluracil
  • 2'-Deoxy-L-thymidine
  • Beta-l-thymidine
  • Epavudine
  • L-deoxythymidine
  • L-DT
  • L-thymidine
  • LDT
  • Telbivudin
  • Telbivudina
  • Telbivudine
  • β-L-2'-deoxythymidine
External IDs
  • LDT-600
  • LDT600
  • NV-02B

Pharmacology

Pharmacology
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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.

Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

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.

TargetActionsOrganism
AProtein PNot AvailableHBV-F
ADNANot AvailableHumans
Absorption

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.

Volume of distribution
Not Available
Protein binding

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

Metabolism

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.

Route of elimination

Telbivudine is eliminated primarily by urinary excretion of unchanged drug.

Half-life

Approximately 15 hours.

Clearance
  • 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)]
Adverse Effects
Medicalerrors
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Toxicity

There is no information on intentional overdose of telbivudine, but one subject experienced an unintentional and asymptomatic overdose. Healthy subjects who received telbivudine doses up to 1800 mg/day for 4 days had no increase in or unexpected adverse events. A maximum tolerated dose for telbivudine has not been determined.

Affected organisms
  • Hepatitis B virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Telbivudine.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Telbivudine.
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Telbivudine.
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Telbivudine.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Telbivudine.
GanciclovirThe risk or severity of cytopenia can be increased when Ganciclovir is combined with Telbivudine.
Human adenovirus e serotype 4 strain cl-68578 antigenThe therapeutic efficacy of Human adenovirus e serotype 4 strain cl-68578 antigen can be decreased when used in combination with Telbivudine.
Interferon alfa-2aThe risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Telbivudine.
Interferon alfa-2bThe risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Telbivudine.
Interferon alfa-n3The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Telbivudine.
Interactions
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Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SebivoTablet, film coated600 mgOralNovartis Europharm Limited2016-09-082021-01-14EU flag
SebivoTabletOralNovartis2006-12-142020-04-21Canada flag
SebivoTablet, film coated600 mgOralNovartis Europharm Limited2016-09-082021-01-14EU flag
SebivoSolution20 mg/mlOralNovartis Europharm Limited2016-09-082021-01-14EU flag
TyzekaTablet, film coated600 mg/1OralNovartis Pharmaceuticals Corporation2006-11-062006-11-06US flag
TyzekaTablet, film coated600 mg/1OralNovartis Pharmaceuticals Corporation2006-10-252018-02-28US flag
TyzekaSolution20 mg/1mLOralNovartis Pharmaceuticals Corporation2009-04-282010-03-01US flag

Categories

ATC Codes
J05AF11 — Telbivudine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Pyrimidine 2'-deoxyribonucleosides
Direct Parent
Pyrimidine 2'-deoxyribonucleosides
Alternative Parents
Pyrimidones / Hydropyrimidines / Vinylogous amides / Tetrahydrofurans / Heteroaromatic compounds / Ureas / Secondary alcohols / Lactams / Oxacyclic compounds / Azacyclic compounds
show 5 more
Substituents
Alcohol / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Lactam / Organic nitrogen compound / Organic oxide / Organic oxygen compound
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrimidine 2'-deoxyribonucleoside (CHEBI:63624)

Chemical Identifiers

UNII
2OC4HKD3SF
CAS number
3424-98-4
InChI Key
IQFYYKKMVGJFEH-CSMHCCOUSA-N
InChI
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
IUPAC Name
1-[(2S,4R,5S)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
CC1=CN([C@@H]2C[C@@H](O)[C@H](CO)O2)C(=O)NC1=O

References

General References
  1. Matthews SJ: Telbivudine for the management of chronic hepatitis B virus infection. Clin Ther. 2007 Dec;29(12):2635-53. doi: 10.1016/j.clinthera.2007.12.032. [PubMed:18201580]
  2. Amarapurkar DN: Telbivudine: a new treatment for chronic hepatitis B. World J Gastroenterol. 2007 Dec 14;13(46):6150-5. [PubMed:18069753]
  3. Dusheiko G, Danta M: Telbivudine for the treatment of chronic hepatitis B. Drugs Today (Barc). 2007 May;43(5):293-304. [PubMed:17724496]
  4. Keam SJ: Telbivudine. Drugs. 2007;67(13):1917-29. [PubMed:17722961]
  5. Ruiz-Sancho A, Sheldon J, Soriano V: Telbivudine: a new option for the treatment of chronic hepatitis B. Expert Opin Biol Ther. 2007 May;7(5):751-61. [PubMed:17477811]
  6. Marcellin P, Asselah T, Boyer N: Treatment of chronic hepatitis B. J Viral Hepat. 2005 Jul;12(4):333-45. [PubMed:15985003]
  7. Han SH: Telbivudine: a new nucleoside analogue for the treatment of chronic hepatitis B. Expert Opin Investig Drugs. 2005 Apr;14(4):511-9. [PubMed:15882124]
  8. Jones R, Nelson M: Novel anti-hepatitis B agents: A focus on telbivudine. Int J Clin Pract. 2006 Oct;60(10):1295-9. [PubMed:16981973]
Human Metabolome Database
HMDB0015394
KEGG Drug
D06675
PubChem Compound
159269
PubChem Substance
46508706
ChemSpider
140081
BindingDB
50088372
RxNav
474128
ChEBI
63624
ChEMBL
CHEMBL374731
ZINC
ZINC000000002159
Therapeutic Targets Database
DAP000698
PharmGKB
PA164760861
PDBe Ligand
LLT
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Telbivudine
AHFS Codes
  • 08:18.32 — Nucleosides and Nucleotides
PDB Entries
3hp1 / 3qeo

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentHepatitis B Chronic Infection1
4CompletedPreventionChronic Infection / Hepatitis B Infection / Viral sepsis1
4CompletedPreventionComplications / Hepatitis B Chronic Infection / Late Pregnancy / Transmission1
4CompletedPreventionHBV1
4CompletedPreventionHepatitis B Chronic Infection1
4CompletedTreatmentChronic Kidney Disease (CKD) / Hepatitis B Chronic Infection1
4CompletedTreatmentCompensated Chronic Hepatitis B1
4CompletedTreatmentComplications, Pregnancy / Elevations in serum alanine aminotransferase (ALT) / Hepatitis B Chronic Infection / High Viral Load1
4CompletedTreatmentHepatitis B Chronic Infection8
4TerminatedTreatmentHBsAg-positive Renal Allograft Recipients1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Idenix Pharmaceutical Inc.
  • Novartis AG
Dosage Forms
FormRouteStrength
SolutionOral20 mg/ml
TabletOral
Tablet, film coatedOral600 mg
Tablet, coatedOral
Tablet, coatedOral600 mg
SolutionOral20 mg/1mL
Tablet, film coatedOral600 mg/1
Prices
Unit descriptionCostUnit
Tyzeka 600 mg tablet27.26USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2340156No2007-10-232019-08-10Canada flag
US6395716No2002-05-282019-08-10US flag
US6444652No2002-09-032019-08-10US flag
US6566344No2003-05-202019-08-10US flag
US6569837No2003-05-272020-10-25US flag
US7589079No2009-09-152023-09-11US flag
US7795238No2010-09-142019-08-10US flag
US7858594No2010-12-282023-09-11US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySparingly soluble in water (>20 mg/mL)Not Available
logP-1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility66.8 mg/mLALOGPS
logP-1.3ALOGPS
logP-1.1ChemAxon
logS-0.56ALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area99.1 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity55.41 m3·mol-1ChemAxon
Polarizability23.25 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.971
Blood Brain Barrier+0.5902
Caco-2 permeable-0.8851
P-glycoprotein substrateNon-substrate0.6468
P-glycoprotein inhibitor INon-inhibitor0.8872
P-glycoprotein inhibitor IINon-inhibitor0.9128
Renal organic cation transporterNon-inhibitor0.9072
CYP450 2C9 substrateNon-substrate0.6893
CYP450 2D6 substrateNon-substrate0.8834
CYP450 3A4 substrateNon-substrate0.5083
CYP450 1A2 substrateNon-inhibitor0.9529
CYP450 2C9 inhibitorNon-inhibitor0.9392
CYP450 2D6 inhibitorNon-inhibitor0.9491
CYP450 2C19 inhibitorNon-inhibitor0.9479
CYP450 3A4 inhibitorNon-inhibitor0.9308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9415
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.7872
BiodegradationNot ready biodegradable0.5131
Rat acute toxicity1.8754 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9358
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
HBV-F
Pharmacological action
Yes
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Multifunctional enzyme that converts the viral RNA genome into dsDNA in viral cytoplasmic capsids. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ri...
Gene Name
P
Uniprot ID
Q05486
Uniprot Name
Protein P
Molecular Weight
94257.43 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Lui YY, Chan HL: Treatment of chronic hepatitis B: focus on telbivudine. Expert Rev Anti Infect Ther. 2009 Apr;7(3):259-68. doi: 10.1586/eri.09.6. [PubMed:19344240]
  4. Nash K: Telbivudine in the treatment of chronic hepatitis B. Adv Ther. 2009 Feb;26(2):155-69. doi: 10.1007/s12325-009-0004-y. Epub 2009 Feb 18. [PubMed:19225726]
  5. Lui YY, Chan HL: A review of telbivudine for the management of chronic hepatitis B virus infection. Expert Opin Drug Metab Toxicol. 2008 Oct;4(10):1351-61. doi: 10.1517/17425255.4.10.1351 . [PubMed:18798704]
  6. Amarapurkar DN: Telbivudine: a new treatment for chronic hepatitis B. World J Gastroenterol. 2007 Dec 14;13(46):6150-5. [PubMed:18069753]
  7. Keam SJ: Telbivudine. Drugs. 2007;67(13):1917-29. [PubMed:17722961]
  8. Ruiz-Sancho A, Sheldon J, Soriano V: Telbivudine: a new option for the treatment of chronic hepatitis B. Expert Opin Biol Ther. 2007 May;7(5):751-61. [PubMed:17477811]
  9. Han SH: Telbivudine: a new nucleoside analogue for the treatment of chronic hepatitis B. Expert Opin Investig Drugs. 2005 Apr;14(4):511-9. [PubMed:15882124]
  10. Jones R, Nelson M: Novel anti-hepatitis B agents: A focus on telbivudine. Int J Clin Pract. 2006 Oct;60(10):1295-9. [PubMed:16981973]
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Nash K: Telbivudine in the treatment of chronic hepatitis B. Adv Ther. 2009 Feb;26(2):155-69. doi: 10.1007/s12325-009-0004-y. Epub 2009 Feb 18. [PubMed:19225726]
  2. Gaeta GB, Stornaiuolo G: Therapy of chronic hepatitis B: focus on telbivudine. Dig Liver Dis. 2007 Nov;39 Suppl 3:S372-8. doi: 10.1016/S1590-8658(07)60017-6. [PubMed:18063258]
  3. Ruiz-Sancho A, Sheldon J, Soriano V: Telbivudine: a new option for the treatment of chronic hepatitis B. Expert Opin Biol Ther. 2007 May;7(5):751-61. [PubMed:17477811]

Drug created on May 16, 2007 17:51 / Updated on March 04, 2021 11:01