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Identification
NameAbacavir
Accession NumberDB01048  (APRD00216)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Abacavir (ABC) is a powerful nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. [Wikipedia] Chemically, it is a synthetic carbocyclic nucleoside and is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. In vivo, abacavir sulfate dissociates to its free base, abacavir.

Structure
Thumb
Synonyms
SynonymLanguageCode
{(1S-cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanolNot AvailableNot Available
AbacavirNot AvailableNot Available
ABC Not AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ziagentablet, film coated300 mgoralREMEDYREPACK INC.2013-04-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Ziagentablet, film coated300 mgoralVii V Healthcare Company1998-12-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Ziagensolution20 mg/mLoralVii V Healthcare Company1999-01-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Ziagentablet, film coated300 mgoralState of Florida DOH Central Pharmacy2009-07-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Ziagentablet300 mgoralViiv Healthcare UlcNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Ziagensolution20 mgoralViiv Healthcare UlcNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Abacavir Sulfatetablet, film coated300 mgoralMylan Pharmaceuticals Inc.2012-08-21Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Abacavirtablet300 mgoralCamber Pharmaceuticals, Inc.2013-09-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Abacavir Sulfatetablet, film coated300 mgoralREMEDYREPACK INC.2013-02-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Abacavir Sulfatetablet, film coated300 mgoralMylan Institutional Inc.2012-08-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Abacavirtablet300 mgoralREMEDYREPACK INC.2014-05-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Abacavir Sulfatetablet, film coated300 mgoralState of Florida DOH Central Pharmacy2013-01-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Abacavir Sulfatetablet, film coated300 mgoralApotex Corp2012-12-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Abacavirtablet, film coated300 mgoralAurobindo Pharma Limited2012-12-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Abacavirtablet, film coated300 mgoralAmerican Health Packaging2013-02-07Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixtures
Brand NameIngredients
EpzicomAbacavir Sulfate + Lamivudine
KivexaAbacavir Sulfate + Lamivudine
TrizivirAbacavir Sulfate + Lamivudine + Zidovudine
Salts
Name/CASStructureProperties
Abacavir Sulfate
188062-50-2
Thumb
  • InChI Key: WMHSRBZIJNQHKT-WOIBLURINA-N
  • Monoisotopic Mass: 670.275797698
  • Average Mass: 670.743
DBSALT000871
Categories
CAS number136470-78-5
WeightAverage: 286.3323
Monoisotopic: 286.154209228
Chemical FormulaC14H18N6O
InChI KeyMCGSCOLBFJQGHM-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
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 1,3-substituted cyclopentyl purine nucleosides. These are nucleoside analogues with a structure that consists of a cyclobutane that is substituted a the 1-position with a hydroxyl group and at the 3-position with either a purine base.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassNucleoside and nucleotide analogues
Sub ClassCyclopentyl nucleosides
Direct Parent1,3-substituted cyclopentyl purine nucleosides
Alternative Parents
Substituents
  • 1,3-substituted cyclopentyl purine nucleoside
  • 6-alkylaminopurine
  • 6-aminopurine
  • Purine
  • Imidazopyrimidine
  • Secondary aliphatic/aromatic amine
  • Aminopyrimidine
  • Imidolactam
  • Pyrimidine
  • Primary aromatic amine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Imidazole
  • Cyclic alcohol
  • Azole
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of HIV-1 infection, in combination with other antiretroviral agents.
PharmacodynamicsAbacavir 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 concentration of drug necessary to effect viral replication by 50 percent (EC50) ranged from 3.7 to 5.8 μM (1 μM = 0.28 mcg/mL) and 0.07 to 1.0 μM against HIV-1IIIB and HIV-1BaL, respectively, and was 0.26 ± 0.18 μM against 8 clinical isolates. Abacavir had synergistic activity in cell culture in combination with the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine, the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, and the protease inhibitor (PI) amprenavir; and additive activity in combination with the NRTIs didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine.
Mechanism of actionAbacavir is a carbocyclic synthetic nucleoside analogue and an antiviral agent. 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. Viral DNA growth is terminated because the incorporated nucleotide lacks a 3'-OH group, which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation.
AbsorptionRapid and extensive after oral administration (83% bioavailability, tablet). When a 300 mg tablet is given twice daily to subjects, the peak plasma concentration (Cmax) was 3.0 ± 0.89 mcg/mL and the area under the curve (AUC 0-12 hours) was 6.02 ± 1.73 mcg•hr/mL.
Volume of distribution
  • 0.86 ± 0.15 L/kg [IV administration]
Protein bindingModerate (approximately 50%). Binding of abacavir to plasma protein was independent of concentration.
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 eliminationElimination 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. Renal excretion of unchanged abacavir is a minor route of elimination in humans.
Half life1.54 ± 0.63 hours
Clearance
  • 0.80 ± 0.24 L/hr/kg [asymptomatic, HIV-1-infected adult patients receiving single (IV dose of 150 mg]
ToxicitySome myocardial degeneration has been noticed in rats and mice. The most commonly reported adverse reactions of at least moderate intensity (incidence ≥10%) in adult HIV-1 clinical trials were nausea, headache, malaise and fatigue, nausea and vomiting, and dreams/sleep disorders. Serious hypersensitivity reactions have been associated with abacavir which has been strongly linked to the presence of the HLA-B*57:01 allele. This reaction manifests itself in patients within the first 6 weeks of treatment. Patients should be tested for the presence of this allele as recommended by the U.S Food and Drug Administration (FDA).
Affected organisms
  • Human Immunodeficiency Virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
HLA class I histocompatibility antigen protein P5
Gene symbol: HCP5
UniProt: Q6MZN7
rs2395029 HLA-B*5701G allelePresence of this SNP is predicative of hypersenitivity reaction when abacavir is given to HIV+ patients.18684101
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9383
Caco-2 permeable-0.5808
P-glycoprotein substrateNon-substrate0.5551
P-glycoprotein inhibitor INon-inhibitor0.9155
P-glycoprotein inhibitor IINon-inhibitor0.6573
Renal organic cation transporterNon-inhibitor0.7734
CYP450 2C9 substrateNon-substrate0.8595
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7376
CYP450 1A2 substrateNon-inhibitor0.538
CYP450 2C9 substrateNon-inhibitor0.8707
CYP450 2D6 substrateNon-inhibitor0.7852
CYP450 2C19 substrateNon-inhibitor0.8667
CYP450 3A4 substrateNon-inhibitor0.559
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8683
Ames testNon AMES toxic0.6662
CarcinogenicityNon-carcinogens0.8649
BiodegradationNot ready biodegradable0.9806
Rat acute toxicity2.4758 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8918
hERG inhibition (predictor II)Non-inhibitor0.8734
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solutionoral20 mg
Solutionoral20 mg/mL
Tabletoral300 mg
Tablet, film coatedoral300 mg
Prices
Unit descriptionCostUnit
Epzicom tablet35.78USD tablet
Ziagen 300 mg tablet10.46USD tablet
Ziagen 20 mg/ml Solution0.7USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada13405891999-06-082016-06-08
Canada22166342004-07-202016-03-28
Canada22897532007-01-232018-05-14
United States50895001992-12-262009-12-26
United States66418432000-02-042020-02-04
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point165 °CNot Available
water solubility77 mg/mL (sulfate salt)FDA label
logP1.20 FDA label
Predicted Properties
PropertyValueSource
Water Solubility1.21 mg/mLALOGPS
logP0.61ALOGPS
logP0.39ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)15.41ChemAxon
pKa (Strongest Basic)5.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area101.88 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity82.62 m3·mol-1ChemAxon
Polarizability30.43 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5034394
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
  2. FDA label
  3. http://pharmgkb.org/pathway/PA166104634#
External Links
ATC CodesJ05AF06
AHFS Codes
  • 08:18.08.20
PDB EntriesNot Available
FDA labelDownload (118 KB)
MSDSDownload (34.7 KB)
Interactions
Drug Interactions
Drug
AtazanavirProtease Inhibitors may decrease the serum concentration of Abacavir.
BatimastatMay decrease the serum concentration of Abacavir.
DarunavirProtease Inhibitors may decrease the serum concentration of Abacavir.
FosamprenavirProtease Inhibitors may decrease the serum concentration of Abacavir.
IndinavirProtease Inhibitors may decrease the serum concentration of Abacavir.
IsoflurophateMay decrease the serum concentration of Abacavir.
LopinavirProtease Inhibitors may decrease the serum concentration of Abacavir.
MethadoneMethadone may diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Methadone.
NelfinavirProtease Inhibitors may decrease the serum concentration of Abacavir.
RibavirinMay enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur.
RitonavirProtease Inhibitors may decrease the serum concentration of Abacavir.
SaquinavirProtease Inhibitors may decrease the serum concentration of Abacavir.
SimeprevirMay decrease the serum concentration of Abacavir.
TipranavirProtease Inhibitors may decrease the serum concentration of Abacavir.
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

Kind: protein

Organism: Human immunodeficiency virus 1

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Reverse transcriptase/RNaseH Q72547 Details

References:

  1. De Clercq E: New anti-HIV agents and targets. Med Res Rev. 2002 Nov;22(6):531-65. Pubmed
  1. Faletto MB, Miller WH, Garvey EP, St Clair MH, Daluge SM, Good SS: Unique intracellular activation of the potent anti-human immunodeficiency virus agent 1592U89. Antimicrob Agents Chemother. 1997 May;41(5):1099-107. Pubmed
  2. Crimmins MT, King BW: An Efficient Asymmetric Approach to Carbocyclic Nucleosides: Asymmetric Synthesis of 1592U89, a Potent Inhibitor of HIV Reverse Transcriptase. J Org Chem. 1996 Jun 26;61(13):4192-4193. Pubmed

Enzymes

1. Alcohol dehydrogenase 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Alcohol dehydrogenase 6 P28332 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-1 P22309 Details

References:

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

3. Adenosine kinase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Adenosine kinase P55263 Details

References:

  1. Faletto MB, Miller WH, Garvey EP, St Clair MH, Daluge SM, Good SS: Unique intracellular activation of the potent anti-human immunodeficiency virus agent 1592U89. Antimicrob Agents Chemother. 1997 May;41(5):1099-107. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:21