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targets (3) transporters (3)
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Identification
Name Lamivudine
Accession Number DB00709 (APRD00681)
Type small molecule
Groups approved
Description

A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Lamivudine [Usan:Ban:Inn]
Salts Not Available
Brand names
Name Company
3TC
Epivir
Epivir-HBV
Hepitec
Heptovir
Zeffix
Brand mixtures
Brand Name Ingredients
Combivir Lamivudine + Zidovudine
Epzicom Abacavir Sulfate + Lamivudine
Kivexa Abacavir Sulfate + Lamivudine
Trizivir Abacavir Sulfate + Lamivudine + Zidovudine
Categories
  • Anti-HIV Agents
  • Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
  • Reverse Transcriptase Inhibitors
CAS number 134678-17-4
Weight Average: 229.256
Monoisotopic: 229.052111923
Chemical Formula C8H11N3O3S
InChI Key InChIKey=JTEGQNOMFQHVDC-NKWVEPMBSA-N
InChI
InChI=1S/C8H11N3O3S/c9-5-1-2-11(8(13)10-5)6-4-15-7(3-12)14-6/h1-2,6-7,12H,3-4H2,(H2,9,10,13)/t6-,7+/m0/s1
Plain Text
IUPAC Name
4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one
SMILES
NC1=NC(=O)N(C=C1)[C@@H]1CS[C@H](CO)O1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyrimidines and Derivatives
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Ethers
  • Oxathiolanes
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Acetals and Derivatives
  • Cyanamides
Pharmacology
Indication For the treatment of HIV infection and chronic hepatitis B (HBV).
Pharmacodynamics Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV). Lamivudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.
Mechanism of action Lamivudine is a synthetic nucleoside analogue and is phosphorylated intracellularly to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP). This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination.
Absorption Lamivudine was rapidly absorbed after oral administration in HIV-infected patients. Absolute bioavailability in adults is 86% ± 16% for the tablet and 87% ± 13% for the oral solution.
Volume of distribution Not Available
Protein binding 36%
Metabolism The only detected metabolite of lamivudine is trans-sulfoxide.
Route of elimination The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase to form the 5′-carboxylic acid and glucuronyl transferase to form the 5′-glucuronide. Lamivudine is excreted in human breast milk and into the milk of lactating rats.
Half life 5 to 7 hours
Clearance
  • Renal cl=280.4 +/- 75.2 mL/min [HIV-infected patients given a single IV doses ranging from 0.25 to 8 mg/kg]
Toxicity Not Available
Affected organisms
  • Human Immunodeficiency Virus
  • Hepatitis B virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Viiv healthcare co
  • Glaxosmithkline
Packagers
Dosage forms
Form Route Strength
Solution Oral
Tablet Oral
Prices
Unit description Cost Unit
Epzicom 600-300 mg tablet 37.21 USD tablet
Epzicom tablet 35.78 USD tablet
Epivir 300 mg tablet 15.57 USD tablet
Epivir hbv 100 mg tablet 13.94 USD tablet
Epivir 150 mg tablet 7.79 USD tablet
Epivir 10 mg/ml Solution 0.53 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6004968 1998-09-20 2018-09-20
United States 7119202 1992-08-08 2009-08-08
Canada 2070230 2004-08-03 2012-06-02
Canada 2100269 1999-02-23 2012-01-03
Properties
State solid
Experimental Properties
Property Value Source
melting point 160-162 °C Not Available
water solubility 70 mg/ml Not Available
logP -1.4 Not Available
Predicted Properties
Property Value Source
water solubility 2.76e+00 g/l ALOGPS
logP -1.3 ALOGPS
logP -1.1 ChemAxon
logS -1.9 ALOGPS
pKa (strongest acidic) 14.29 ChemAxon
pKa (strongest basic) -0.16 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 88.15 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 55.16 ChemAxon
polarizability 21.7 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Fox Z, Dragsted UB, Gerstoft J, Phillips AN, Kjaer J, Mathiesen L, Youle M, Katlama C, Hill A, Bruun JN, Clumeck N, Dellamonica P, Lundgren JD: A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial. Antivir Ther. 2006;11(6):761-70. Pubmed
External Links
Resource Link
KEGG Drug D00353 Link_out
KEGG Compound C07065 Link_out
PubChem Compound 60825 Link_out
PubChem Substance 46507855 Link_out
ChemSpider 54812 Link_out
BindingDB 50046287 Link_out
Therapeutic Targets Database DAP000167 Link_out
PharmGKB PA450163 Link_out
Drug Product Database 2239194 Link_out
RxList http://www.rxlist.com/cgi/generic3/lamivudine.htm Link_out
Drugs.com http://www.drugs.com/cdi/lamivudine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/com1513.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Lamivudine Link_out
ATC Codes
  • J05AF05
AHFS Codes
  • 08:18.08.20
PDB Entries Not Available
FDA label show (310 KB)
MSDS show (57.6 KB)
Interactions
Drug Interactions
Drug Interaction
Tobramycin Increased risk of nephrotoxicity
Valganciclovir The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Lamivudine, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.
Zalcitabine Lamivudine may reduce the efficacy of zalcitabine. Combination therapy is not recommended.
Food Interactions
  • Take without regard to meals. Food does not decrease the extent of absorption, but it decreases the Cmax by slowing the rate of absorption.
Targets

1. Reverse transcriptase

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q5DNL9 Link_out

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
  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

2. DNA

Pharmacological action: yes
Actions: adduct

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.

Gene Sequence: FASTA

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
  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
  3. Pan XP, Li LJ, Du WB, Li MW, Cao HC, Sheng JF: Differences of YMDD mutational patterns, precore/core promoter mutations, serum HBV DNA levels in lamivudine-resistant hepatitis B genotypes B and C. J Viral Hepat. 2007 Nov;14(11):767-74. Pubmed
  4. Dai CY, Yu ML, Hsieh MY, Lee LP, Hou NJ, Huang JF, Chen SC, Lin ZY, Hsieh MY, Wang LY, Tsai JF, Chang WY, Chuang WL: Early response to lamivudine therapy in clinically non-cirrhotic chronic hepatitis B patients with decompensation. Liver Int. 2007 Sep 27;. Pubmed
  5. Ma H, Guo F, Wei L, Sun Y, Wang H: [The prospective study of the clinical features and outcome of HBeAg-negative and HBeAg-positive cirrhosis in patients with chronic type B hepatitis] Zhonghua Yi Xue Za Zhi. 2007 Jul 10;87(26):1832-5. Pubmed

3. P protein [Includes: DNA-directed DNA polymerase

Pharmacological action: yes
Actions: inhibitor
Organism class: viral
UniProt ID: Q05486 Link_out
Gene: P
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Stuyver LJ, Locarnini SA, Lok A, Richman DD, Carman WF, Dienstag JL, Schinazi RF: Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region. Hepatology. 2001 Mar;33(3):751-7. Pubmed
Transporters

1. Multidrug resistance-associated protein 1

Actions: inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Olson DP, Scadden DT, D’Aquila RT, De Pasquale MP: The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related-protein 1 (MRP-1). AIDS. 2002 Sep 6;16(13):1743-7. Pubmed

2. Solute carrier family 22 member 6

Actions: substrate
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. Pubmed

3. ATP-binding cassette sub-family G member 2

Actions: substrate

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19