Telbivudine

Overview

Description
A medication used to treat hepatitis.
Description
A medication used to treat hepatitis.
DrugBank ID
DB01265
Type
Small Molecule
US Approved
YES
Other Approved
YES
Clinical Trials
Phase 0
0
Phase 1
4
Phase 2
8
Phase 3
17
Phase 4
35
Therapeutic Categories
  • Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor
  • Nucleosides and Nucleotides
Mechanism of Action

Identification

Summary

Telbivudine is a thymidine nucleoside analog used for the treatment of chronic hepatitis B with clinical evidence of viral replication or persistent elevations in serum aminotransferases (ALT or AST).

Generic Name
Telbivudine
DrugBank Accession Number
DB01265
Background

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
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

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.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofChronic hepatitis b••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
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
ADNANot AvailableHumans
AProtein PNot AvailableHBV-F
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
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
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.

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 russian BCG-I live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain russian BCG-I 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.
Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SebivoSolution20 mg/mlOralNovartis Europharm Limited2016-09-082007-02-22EU flag
SebivoTablet600 mgOralNovartis2006-12-142020-04-21Canada flag
SebivoTablet, film coated600 mgOralNovartis Europharm Limited2016-09-082007-02-22EU flag
SebivoTablet, film coated600 mgOralNovartis Europharm Limited2016-09-082007-02-22EU flag
TyzekaTablet, film coated600 mg/1OralNovartis Farma S.P.A.2006-10-252018-02-28US 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)
Affected organisms
  • Hepatitis B virus

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. [Article]
  2. Amarapurkar DN: Telbivudine: a new treatment for chronic hepatitis B. World J Gastroenterol. 2007 Dec 14;13(46):6150-5. [Article]
  3. Dusheiko G, Danta M: Telbivudine for the treatment of chronic hepatitis B. Drugs Today (Barc). 2007 May;43(5):293-304. [Article]
  4. Keam SJ: Telbivudine. Drugs. 2007;67(13):1917-29. [Article]
  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. [Article]
  6. Marcellin P, Asselah T, Boyer N: Treatment of chronic hepatitis B. J Viral Hepat. 2005 Jul;12(4):333-45. [Article]
  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. [Article]
  8. Jones R, Nelson M: Novel anti-hepatitis B agents: A focus on telbivudine. Int J Clin Pract. 2006 Oct;60(10):1295-9. [Article]
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
PDB Entries
3qeo

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableChronic Hepatitis B Infection1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableHBeAg Positive Chronic Hepatitis B Infection1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentSpontaneous Reactivation of Hepatitis B1somestatusstop reasonjust information to hide
Not AvailableUnknown StatusNot AvailableImmune Globulin, Prophylaxis, Telbuvidine, Vaccine1somestatusstop reasonjust information to hide
Not AvailableUnknown StatusNot AvailableThe Safety of Anti-viral Drugs Used in Late Pregnancy1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Idenix Pharmaceutical Inc.
  • Novartis AG
Dosage Forms
FormRouteStrength
SolutionOral20 mg/ml
TabletOral600 mg
Tablet, film coatedOral600 MG
Tablet, coatedOral600 mg
Tablet, film coatedOral600.0 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
Polarizability23.2 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-MSsplash10-0006-9420000000-ebaddd47fbf973a127a1
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0032-9400000000-50b49c62fd5b3e635e9e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ukc-0970000000-64f2ff121c49344e6c01
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-053s-9100000000-ea604ff67cec7cb3e665
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9600000000-963395937553c2145ab6
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-5900000000-e6f0bdfe8c34585c5fde
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-7900000000-67dec2d0a453354ed865
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-159.1906703
predicted
DarkChem Lite v0.1.0
[M-H]-161.4513703
predicted
DarkChem Lite v0.1.0
[M-H]-159.4537703
predicted
DarkChem Lite v0.1.0
[M-H]-158.50969
predicted
DeepCCS 1.0 (2019)
[M+H]+160.4882703
predicted
DarkChem Lite v0.1.0
[M+H]+164.8653703
predicted
DarkChem Lite v0.1.0
[M+H]+159.6535703
predicted
DarkChem Lite v0.1.0
[M+H]+160.90578
predicted
DeepCCS 1.0 (2019)
[M+Na]+159.1829703
predicted
DarkChem Lite v0.1.0
[M+Na]+160.8793703
predicted
DarkChem Lite v0.1.0
[M+Na]+159.4876703
predicted
DarkChem Lite v0.1.0
[M+Na]+166.86752
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
HBV-F
Pharmacological action
Yes
General 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 ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3'- to 5'-endonucleasic mode. Neo-synthesized pregenomic RNA (pgRNA) are encapsidated together with the P protein, and reverse-transcribed inside the nucleocapsid. Initiation of reverse-transcription occurs first by binding the epsilon loop on the pgRNA genome, and is initiated by protein priming, thereby the 5'-end of (-)DNA is covalently linked to P protein. Partial (+)DNA is synthesized from the (-)DNA template and generates the relaxed circular DNA (RC-DNA) genome. After budding and infection, the RC-DNA migrates in the nucleus, and is converted into a plasmid-like covalently closed circular DNA (cccDNA). The activity of P protein does not seem to be necessary for cccDNA generation, and is presumably released from (+)DNA by host nuclear DNA repair machinery.
Specific Function
DNA binding
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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 . [Article]
  6. Amarapurkar DN: Telbivudine: a new treatment for chronic hepatitis B. World J Gastroenterol. 2007 Dec 14;13(46):6150-5. [Article]
  7. Keam SJ: Telbivudine. Drugs. 2007;67(13):1917-29. [Article]
  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. [Article]
  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. [Article]
  10. Jones R, Nelson M: Novel anti-hepatitis B agents: A focus on telbivudine. Int J Clin Pract. 2006 Oct;60(10):1295-9. [Article]

Drug created at May 16, 2007 17:51 / Updated at November 06, 2024 16:18