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Identification
NameTelbivudine
Accession NumberDB01265
TypeSmall Molecule
GroupsApproved, Investigational
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.

Structure
Thumb
Synonyms
1-(2-Deoxy-beta-L-ribofuranosyl)-5-methyluracil
2'-Deoxy-L-thymidine
beta-L-2'-Deoxythymidine
Beta-l-thymidine
Epavudine
L-deoxythymidine
L-DT
L-thymidine
LDT
Telbivudin
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sebivotablet600 mgoralNovartis Pharmaceuticals Canada Inc2006-12-14Not applicableCanada
Tyzekatablet, film coated600 mg/1oralNovartis Pharmaceuticals Corporation2006-10-25Not applicableUs
Tyzekasolution20 mg/mLoralNovartis Pharmaceuticals Corporation2009-04-28Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII2OC4HKD3SF
CAS number3424-98-4
WeightAverage: 242.2286
Monoisotopic: 242.090271568
Chemical FormulaC10H14N2O5
InChI KeyInChIKey=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)[[email protected]](CO)O2)C(=O)NC1=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPyrimidine nucleosides
Sub ClassPyrimidine 2'-deoxyribonucleosides
Direct ParentPyrimidine 2'-deoxyribonucleosides
Alternative Parents
Substituents
  • Pyrimidine 2'-deoxyribonucleoside
  • Pyrimidone
  • Pyrimidine
  • Hydropyrimidine
  • Saccharide
  • Heteroaromatic compound
  • Vinylogous amide
  • Oxolane
  • Urea
  • Secondary alcohol
  • Lactam
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsTelbivudine 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 actionTelbivudine 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.
Related Articles
AbsorptionAbsorbed 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 distributionNot Available
Protein bindingIn 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 eliminationTelbivudine is eliminated primarily by urinary excretion of unchanged drug.
Half lifeApproximately 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)]
ToxicityThere 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral600 mg
Solutionoral20 mg/mL
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)
CA2340156 No2007-10-232019-08-10Canada
US6395716 No1999-08-102019-08-10Us
US6444652 No1999-08-102019-08-10Us
US6566344 No1999-08-102019-08-10Us
US6569837 No2000-10-252020-10-25Us
US7589079 No2003-09-112023-09-11Us
US7795238 No1999-08-102019-08-10Us
US7858594 No2003-09-112023-09-11Us
Properties
StateSolid
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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis ReferenceNot Available
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 ]
External Links
ATC CodesJ05AF11
AHFS Codes
  • 08:18.08.20
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Interferon Alfa-2b, RecombinantThe risk or severity of adverse effects can be increased when Interferon Alfa-2b, Recombinant is combined with Telbivudine.
Peginterferon alfa-2aThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Telbivudine.
Peginterferon alfa-2bThe risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Telbivudine.
Food Interactions
  • Take without regard to meals.

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 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 to...
Gene Name:
P
Uniprot ID:
Q05486
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 ]
2. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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 ]
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Drug created on May 16, 2007 11:51 / Updated on July 28, 2016 01:50