Telbivudine

Identification

Name
Telbivudine
Accession Number
DB01265
Type
Small Molecule
Groups
Approved, 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 IDs
LDT-600 / LDT600
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SebivoTablet, film coated600 mgOralNovartis Europharm Limited2007-04-24Not applicableEu
SebivoSolution20 mg/mlOralNovartis Europharm Limited2007-04-24Not applicableEu
SebivoTablet600 mgOralNovartis2006-12-14Not applicableCanada
SebivoTablet, film coated600 mgOralNovartis Europharm Limited2007-04-24Not applicableEu
TyzekaSolution20 mg/mLOralNovartis2009-04-282016-12-07Us
TyzekaTablet, film coated600 mg/1OralNovartis2006-10-252018-02-28Us
Categories
UNII
2OC4HKD3SF
CAS number
3424-98-4
Weight
Average: 242.2286
Monoisotopic: 242.090271568
Chemical Formula
C10H14N2O5
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([[email protected]@H]2C[[email protected]@H](O)[[email protected]](CO)O2)C(=O)NC1=O

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.

Structured Indications
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 AvailableHuman
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)]
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
DrugInteractionDrug group
Interferon Alfa-2b, RecombinantThe risk or severity of adverse effects can be increased when Interferon Alfa-2b, Recombinant is combined with Telbivudine.Approved
Peginterferon alfa-2aThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Telbivudine.Approved, Investigational
Peginterferon alfa-2bThe risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Telbivudine.Approved
Food Interactions
  • Take without regard to meals.

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]
External Links
Human Metabolome Database
HMDB15394
PubChem Compound
159269
PubChem Substance
46508706
ChemSpider
140081
BindingDB
50156567
ChEBI
63624
ChEMBL
CHEMBL374731
Therapeutic Targets Database
DAP000698
PharmGKB
PA164760861
HET
LLT
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
ATC Codes
J05AF11 — Telbivudine
AHFS Codes
  • 08:18.32 — Nucleosides and Nucleotides
PDB Entries
3hp1 / 3qeo

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableChronic Hepatitis B Infection1
1, 2Active Not RecruitingTreatmentHepatitis B,Chronic1
1, 2Not Yet RecruitingTreatmentChronic Hepatitis B Infection1
2CompletedTreatmentChronic Hepatitis B Infection1
2CompletedTreatmentViral Hepatitis B2
2, 3CompletedTreatmentDisorder Related to Transplantation / Injury Due to Exposure to External Cause / Virus Diseases1
3Active Not RecruitingTreatmentChronic Hepatitis B Infection1
3CompletedOtherHepatitis B,Chronic1
3CompletedTreatmentChronic Hepatitis B Infection4
3CompletedTreatmentChronic Hepatitis B Infection / Viral Hepatitis B1
3CompletedTreatmentChronic Viral Hepatitis B Without Delta-agent1
3CompletedTreatmentHepatitis B Virus (HBV)1
3CompletedTreatmentHepatitis / Hepatitis B,Chronic / Liver Cirrhosis1
3CompletedTreatmentLiver Cirrhosis / Viral Hepatitis B1
3TerminatedTreatmentViral Hepatitis B2
3Unknown StatusTreatmentChronic Hepatitis B Infection1
4Active Not RecruitingTreatmentHepatitis B,Chronic1
4CompletedPreventionChronic Hepatitis B Infection / Complications / Late Pregnancy / Transmission1
4CompletedPreventionChronic Infection / Hepatitis B Infection / Viral sepsis1
4CompletedPreventionHBV1
4CompletedTreatmentChronic Hepatitis B Infection3
4CompletedTreatmentChronic Hepatitis B Infection / Complications, Pregnancy / Elevated Alanine Aminotransferase Levels / High Viral Load1
4CompletedTreatmentCompensated Chronic Hepatitis B1
4CompletedTreatmentHepatitis B,Chronic5
4RecruitingTreatmentChronic Hepatitis B Infection1
4TerminatedTreatmentHBsAg-positive Renal Allograft Recipients1
4TerminatedTreatmentHepatitis, Chronic1
4Unknown StatusTreatmentChronic Hepatitis B Infection3
4Unknown StatusTreatmentChronic Hepatitis B Infection / Liver Cirrhosis1
4Unknown StatusTreatmentChronic Hepatitis B, Gestation1
4Unknown StatusTreatmentHBV-related Liver Cirrhosis1
4Unknown StatusTreatmentHepatitis B,Chronic2
4Unknown StatusTreatmentHepatocellular,Carcinoma1
4WithdrawnTreatmentChronic Hepatitis B Infection2
4WithdrawnTreatmentCompensated Chronic Hepatitis B1
4WithdrawnTreatmentHepatitis B,Chronic1
Not AvailableCompletedNot AvailableChronic Hepatitis B Infection1
Not AvailableCompletedNot AvailableHBeAg Positive Chronic Hepatitis B Infection1
Not AvailableCompletedTreatmentSpontaneous Reactivation of Hepatitis B1
Not AvailableEnrolling by InvitationNot AvailableThe Safety of Anti-viral Drugs Used in Late Pregnancy1
Not AvailableUnknown StatusNot AvailableImmune Globulin, Prophylaxis, Telbuvidine, Vaccine1
Not AvailableUnknown StatusTreatmentHepatitis B Virus (HBV)1
Not AvailableWithdrawnTreatmentChronic Hepatitis B Infection2
Not AvailableWithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections / Viral Hepatitis B1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
TabletOral600 mg
Tablet, film coatedOral600 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)
CA2340156No2007-10-232019-08-10Canada
US6395716No1999-08-102019-08-10Us
US6444652No1999-08-102019-08-10Us
US6566344No1999-08-102019-08-10Us
US6569837No2000-10-252020-10-25Us
US7589079No2003-09-112023-09-11Us
US7795238No1999-08-102019-08-10Us
US7858594No2003-09-112023-09-11Us

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

Taxonomy

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
Pyrimidine 2'-deoxyribonucleoside / Pyrimidone / Hydropyrimidine / Pyrimidine / Heteroaromatic compound / Tetrahydrofuran / Vinylogous amide / Lactam / Secondary alcohol / Urea
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrimidine 2'-deoxyribonucleoside (CHEBI:63624)

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]
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]

Drug created on May 16, 2007 11:51 / Updated on January 14, 2018 10:04