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Identification
Name Abacavir
Accession Number DB01048 (APRD00216)
Type small molecule
Groups approved
Description

Abacavir (ABC) is a powerful nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Ziagen
Brand mixtures
Brand Name Ingredients
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 136470-78-5
Weight Average: 286.3323
Monoisotopic: 286.154209228
Chemical Formula C14H18N6O
InChI Key InChIKey=MCGSCOLBFJQGHM-SCZZXKLOSA-N
InChI
InChI=1S/C14H18N6O/c15-14-18-12(17-9-2-3-9)11-13(19-14)20(7-16-11)10-4-1-8(5-10)6-21/h1,4,7-10,21H,2-3,5-6H2,(H3,15,17,18,19)/t8-,10+/m1/s1
Plain Text
IUPAC Name
[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl]methanol
SMILES
NC1=NC2=C(N=CN2[C@@H]2C[C@H](CO)C=C2)C(NC2CC2)=N1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Purines and Purine Derivatives
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Aliphatic and Aryl Amines
  • Cyclopropane and Derivatives
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
Pharmacology
Indication For the treatment of HIV-1 infection, in combination with other antiretroviral agents.
Pharmacodynamics Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Abacavir 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 Abacavir is a carbocyclic synthetic nucleoside analogue. Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate, an analogue of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.
Absorption Rapid and extensive after oral administration (83% bioavailability)
Volume of distribution
  • 0.86 ± 0.15 L/kg
Protein binding Moderate (approximately 50%)
Metabolism Hepatic, by alcohol dehydrogenase and glucuronosyltransferase to a 5′-carboxylic acid metabolite and 5′-glucuronide metabolite, respectively. These metabolites have no antiviral activity. Abacavir is not significantly metabolized by cytochrome P450 enzymes.
Route of elimination Elimination of abacavir was quantified in a mass balance study following administration of a 600-mg dose of 14C-abacavir: 99% of the radioactivity was recovered, 1.2% was excreted in the urine as abacavir, 30% as the 5′-carboxylic acid metabolite, 36% as the 5′-glucuronide metabolite, and 15% as unidentified minor metabolites in the urine. Fecal elimination accounted for 16% of the dose. Fecal elimination accounted for 16% of the dose. Renal excretion of unchanged abacavir is a minor route of elimination in humans.
Half life 1.54 ± 0.63 hours
Clearance
  • 0.80 +/- 0.24 L/hr/kg [asymptomatic, HIV-1-infected adult patients receiving single (IV dose of 150 mg]
Toxicity Some myocardial degeneration has been noticed in rats and mice
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Viiv healthcare co
Packagers
Dosage forms
Form Route Strength
Solution Oral
Tablet Oral
Prices
Unit description Cost Unit
Epzicom tablet 35.78 USD tablet
Ziagen 300 mg tablet 10.46 USD tablet
Ziagen 20 mg/ml Solution 0.7 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 6641843 2000-02-04 2020-02-04
United States 5089500 1992-12-26 2009-12-26
Canada 2289753 2007-01-23 2018-05-14
Canada 1340589 1999-06-08 2016-06-08
Properties
State solid
Experimental Properties
Property Value Source
melting point 165 °C Not Available
water solubility 77 mg/mL (sulfate salt) Not Available
logP 1.1 Not Available
Predicted Properties
Property Value Source
water solubility 1.21e+00 g/l ALOGPS
logP 0.61 ALOGPS
logP 0.39 ChemAxon
logS -2.4 ALOGPS
pKa (strongest acidic) 15.41 ChemAxon
pKa (strongest basic) 5.77 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 101.88 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 82.62 ChemAxon
polarizability 30.43 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Zucman D, Truchis P, Majerholc C, Stegman S, Caillat-Zucman S: Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population. J Acquir Immune Defic Syndr. 2007 May 1;45(1):1-3. Pubmed
External Links
Resource Link
KEGG Drug D07057 Link_out
KEGG Compound C07624 Link_out
PubChem Compound 441300 Link_out
PubChem Substance 46505718 Link_out
ChemSpider 58649 Link_out
ChEBI 2360 Link_out
ChEMBL 2360 Link_out
Therapeutic Targets Database DAP000704 Link_out
PharmGKB PA448004 Link_out
Drug Product Database 2240358 Link_out
RxList http://www.rxlist.com/cgi/generic/abavir.htm Link_out
Drugs.com http://www.drugs.com/cdi/abacavir.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cx1527.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Abacavir Link_out
ATC Codes
  • J05AF06
AHFS Codes
  • 08:18.08.20
PDB Entries Not Available
FDA label show (118 KB)
MSDS show (34.7 KB)
Interactions
Drug Interactions
Drug Interaction
Amprenavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Amprenavir. The antiviral response should be closely monitored.
Atazanavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Atazanavir. The antiviral response should be closely monitored.
Darunavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Darunavir. The antiviral response should be closely monitored.
Ethanol Abacavir is partly metabolized through the alcohol dehydrogenase enzyme system. Alcohol increases the area under the curve (about 41%) of Abacavir. Interaction does not appear to be clinically significant.
Fosamprenavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Fosamprenavir. The antiviral response should be closely monitored.
Ganciclovir The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Ganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is required.
Indinavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Indinavir. The antiviral response should be closely monitored.
Lopinavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Lopinavir. The antiviral response should be closely monitored.
Nelfinavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Nelfinavir. The antiviral response should be closely monitored.
Ribavirin Ribavirin may increase the hepatotoxicity of reverse transcriptase inhibitors (nucleoside) such as Abacavir. Lactic acidosis may occur. Consider modifying therapy.
Ribavirin Monophosphate Ribavirin Monophosphate may increase the hepatotoxicity of reverse transcriptase inhibitors (nucleoside) such as Abacavir. Lactic acidosis may occur. Consider modifying therapy.
Ritonavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Ritonavir. The antiviral response should be closely monitored.
Saquinavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Saquinavir. The antiviral response should be closely monitored.
Tipranavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Tipranavir. The antiviral response should be closely monitored.
Valganciclovir The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.
Food Interactions
  • Abacavir is partly metabolised through the alcohol-dehydrogenase enzyme system.
  • Alcohol significantly increases abacavir's area under the curve (about 41%).
  • Avoid alcohol.
  • Take without regard to meals.
Targets

1. Reverse transcriptase

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

References:
  1. De Clercq E: New anti-HIV agents and targets. Med Res Rev. 2002 Nov;22(6):531-65. Pubmed
  2. Lewis RJ, Tsai FT, Wigley DB: Molecular mechanisms of drug inhibition of DNA gyrase. Bioessays. 1996 Aug;18(8):661-71. Pubmed
Enzymes

1. Alcohol dehydrogenase 6

An alcohol + NAD(+) = an aldehyde or ketone + NADH

UniProt ID: P28332 Link_out
Gene: ADH6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yuen GJ, Weller S, Pakes GE: A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351-71. Pubmed

2. UDP-glucuronosyltransferase 1-1

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate

UniProt ID: P22309 Link_out
Gene: UGT1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yuen GJ, Weller S, Pakes GE: A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351-71. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19