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Identification
Name Emtricitabine
Accession Number DB00879 (APRD00226)
Type small molecule
Groups approved
Description

Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) for the treatment of HIV infection in adults. Emtricitabine is an analogue of cytidine. The drug works by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • emtricitabine
Brand names
  • Coviracil
  • Emtriva
  • Racivir
Brand name mixtures
  • Sustiva (emtricitabine + tenofovir + efavarenz)
  • Truvada (emtricitabine + tenofovir disproxil)
Categories
  • Antiviral Agents
  • Anti-HIV Agents
CAS number 143491-57-0
Weight Average: 247.247
Monoisotopic: 247.042690096
Chemical Formula C8H10FN3O3S
InChI Key InChIKey=XQSPYNMVSIKCOC-NTSWFWBYSA-N
InChI
InChI=1S/C8H10FN3O3S/c9-4-1-12(8(14)11-7(4)10)5-3-16-6(2-13)15-5/h1,5-6,13H,2-3H2,(H2,10,11,14)/t5-,6+/m0/s1
Plain Text
IUPAC Name
4-amino-5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one
SMILES
NC1=NC(=O)N(C=C1F)[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
  • Aryl Halides
Pharmacology
Indication Indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults and for postexposure prophylaxis of HIV infection in health care workers and others exposed occupationally or nonoccupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.
Pharmacodynamics Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Emtricitabine helps to block HIV reverse transcriptase, a chemical in your body (enzyme) that is needed for HIV to multiply. Emtricitabine is always used with other anti-HIV medicines to treat people with HIV infection. Emtricitabine may lower the amount of HIV in the blood (viral load). Emtricitabine may also help to increase the number of T cells called CD4 cells. Lowering the amount of HIV in the blood lowers the chance of death or infections that happen when your immune system is weak (opportunistic infections). People taking emtricitabine may still get opportunistic infections or other conditions that happen with HIV infection.
Mechanism of action Emtricitabine works by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA. Emtricitabine is a synthetic nucleoside analogue of cytidine. It is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate, which is responsible for the inhibition of HIV-1 reverse transcriptase. It competes with the natural substrate deoxycytidine 5'-triphosphate and incorporates into nascent viral DNA, resulting in early chain termination. Therefore emtricitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate deoxycytidine 5'-triphosphate and by its incorporation into viral DNA. By inhibiting HIV-1 reverse transcriptase, emtricitabine can help to lower the amount of HIV, or "viral load", in a patient's body and can indirectly increase the number of immune system cells (called T cells or CD4+ T-cells). Both of these changes are associated with healthier immune systems and decreased likelihood of serious illness.
Absorption Rapidly absorbed (mean absolute bioavailability of 93% for capsules, and 75% for solution). Food does not effect absorption.
Volume of distribution Not Available
Protein binding Very low (less than 4%)
Metabolism

Minimally transformed (13%), most appears unchanged in urine (86%). The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3′-sulfoxide diastereomers (~ 9% of dose) and conjugation with glucuronic acid to form 2′-O-glucuronide (~ 4% of dose). In vitro studies indicate emtricitabine is not an inhibitor or cytochrome P450 enzymes.
Route of elimination The renal clearance of emtricitabine is greater than the estimated creatinine clearance, suggesting elimination by both glomerular filtration and active tubular secretion.
Half life 10 hours
Clearance
  • 302 +/- 94 mL/min [Renal Function Creatinine Clearance>80 ml/min]
  • 168 +/- 10 mL/min [Renal Function Creatinine Clearance 50-80 ml/min]
  • 138 +/- 28 mL/min [Renal Function Creatinine Clearance 30-49 ml/min]
  • 99 +/- 6 mL/min [Renal Function Creatinine Clearance<30 ml/min]
  • 64 +/- 12 mL/min [ESRD patients requiring dialysis]
Toxicity Symptoms of overdose include serious liver problems (hepatotoxicity, with liver enlargement and fat in the liver called steatosis) or a lactic acidosis (buildup of an acid in the blood).
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Gilead sciences inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Emtriva 200 mg capsule 21.75 USD capsule
Patents
Country Patent Number Approved Expires
United States 6703396 2001-09-09 2021-09-09
United States 7402588 1993-02-01 2010-02-01
Canada 2075189 2004-11-30 2011-01-31
Properties
State solid
Melting point 136-140 oC
Experimental Properties
Property Value Source
water solubility 112 mg/mL PhysProp
logP -1.4 PhysProp
pKa 2.65 Various sources
Predicted Properties
Property Value Source
water solubility 2.00e+00 g/l ALOGPS
logP -0.80 ALOGPS
logP -0.90 ChemAxon Molconvert
logS -2.09 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 88.15 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 55.37 ChemAxon Molconvert
polarizability 21.79 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Masho SW, Wang CL, Nixon DE: Review of tenofovir-emtricitabine. Ther Clin Risk Manag. 2007 Dec;3(6):1097-104. Pubmed
  2. Long MC, King JR, Acosta EP: Pharmacologic aspects of new antiretroviral drugs. Curr HIV/AIDS Rep. 2009 Feb;6(1):43-50. Pubmed
  3. Emtricitabine/tenofovir disoproxil fumarate. Drugs R D. 2004;5(3):160-1. Pubmed
  4. Goicoechea M, Best B: Efavirenz/emtricitabine/tenofovir disoproxil fumarate fixed-dose combination: first-line therapy for all? Expert Opin Pharmacother. 2007 Feb;8(3):371-82. Pubmed
External Links
Resource Link
KEGG Drug D01199 Link_out
KEGG Compound C12599 Link_out
PubChem Compound 60877 Link_out
PubChem Substance 46507606 Link_out
ChemSpider 54859 Link_out
BindingDB 50046283 Link_out
ChEBI 31536 Link_out
ChEMBL 31536 Link_out
Therapeutic Targets Database DAP001084 Link_out
PharmGKB PA10069 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic3/emtriva.htm Link_out
Drugs.com http://www.drugs.com/cdi/emtricitabine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Emtricitabine Link_out
ATC Codes
  • J05AF09
AHFS Codes
  • 08:18.08.20
PDB Entries Not Available
FDA label show (328.2 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
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
  3. Nirogi R, Bhyrapuneni G, Kandikere V, Mudigonda K, Komarneni P, Aleti R, Mukkanti K: Simultaneous quantification of a non-nucleoside reverse transcriptase inhibitor efavirenz, a nucleoside reverse transcriptase inhibitor emtricitabine and a nucleotide reverse transcriptase inhibitor tenofovir in plasma by liquid chromatography positive ion electrospray tandem mass spectrometry. Biomed Chromatogr. 2009 Apr;23(4):371-81. Pubmed
  4. Feng JY, Ly JK, Myrick F, Goodman D, White KL, Svarovskaia ES, Borroto-Esoda K, Miller MD: The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study. Retrovirology. 2009 May 13;6:44. Pubmed
  5. Delahunty T, Bushman L, Robbins B, Fletcher CV: The simultaneous assay of tenofovir and emtricitabine in plasma using LC/MS/MS and isotopically labeled internal standards. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jul 1;877(20-21):1907-14. Epub 2009 May 21. Pubmed
  6. Emtricitabine/tenofovir disoproxil fumarate. Drugs R D. 2004;5(3):160-1. Pubmed
  7. Goicoechea M, Best B: Efavirenz/emtricitabine/tenofovir disoproxil fumarate fixed-dose combination: first-line therapy for all? Expert Opin Pharmacother. 2007 Feb;8(3):371-82. Pubmed
  8. Perry CM: Emtricitabine/tenofovir disoproxil fumarate: in combination with a protease inhibitor in HIV-1 infection. Drugs. 2009;69(7):843-57. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.