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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
{(1S-cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol
Abacavir
ABC
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ziagentablet, film coated300 mg/1oralREMEDYREPACK INC.2013-04-08Not applicableUs
Ziagensolution20 mgoralViiv Healthcare Ulc1999-06-15Not applicableCanada
Ziagentablet300 mgoralViiv Healthcare Ulc1999-06-09Not applicableCanada
Ziagentablet, film coated300 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Ziagensolution20 mg/mLoralVii V Healthcare Company1999-01-28Not applicableUs
Ziagentablet, film coated300 mg/1oralVii V Healthcare Company1998-12-29Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Abacavirtablet, film coated300 mg/1oralAmerican Health Packaging2013-02-07Not applicableUs
Abacavirtablet, film coated300 mg/1oralAurobindo Pharma Limited2012-12-17Not applicableUs
Abacavirtablet300 mg/1oralREMEDYREPACK INC.2014-05-29Not applicableUs
Abacavirtablet300 mg/1oralCamber Pharmaceuticals, Inc.2013-09-18Not applicableUs
Abacavir Sulfatetablet, film coated300 mg/1oralMylan Pharmaceuticals Inc.2012-06-19Not applicableUs
Abacavir Sulfatetablet, film coated300 mg/1oralApotex Corp2012-12-17Not applicableUs
Abacavir Sulfatetablet, film coated300 mg/1oralState of Florida DOH Central Pharmacy2013-01-01Not applicableUs
Abacavir Sulfatetablet, film coated300 mg/1oralMylan Institutional Inc.2012-08-01Not applicableUs
Abacavir Sulfatetablet, film coated300 mg/1oralREMEDYREPACK INC.2013-02-272016-04-05Us
Apo-abacavirtablet300 mgoralApotex Inc2016-03-15Not applicableCanada
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Abacavir Sulfate, Lamivudine and ZidovudineLupin Pharmaceuticals, Inc.
Apo-abacavir-lamivudineApotex Inc
Apo-abacavir-lamivudine-zidovudineApotex Inc
EpzicomREMEDYREPACK INC.
KivexaViiv Healthcare Ulc
Mylan-abacavir/lamivudineMylan Pharmaceuticals Ulc
Teva-abacavir/lamivudineTeva Canada Limited
TriumeqVii V Healthcare Company
TrizivirVii V Healthcare Company
Salts
Name/CASStructureProperties
Abacavir Sulfate
188062-50-2
Thumb
  • InChI Key: WMHSRBZIJNQHKT-WOIBLURINA-N
  • Monoisotopic Mass: 670.275797698
  • Average Mass: 670.743
DBSALT000871
Categories
UNIIWR2TIP26VS
CAS number136470-78-5
WeightAverage: 286.3323
Monoisotopic: 286.154209228
Chemical FormulaC14H18N6O
InChI KeyInChIKey=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
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[[email protected]](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.
Related Articles
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
Pathways
PathwayCategorySMPDB ID
Abacavir Action PathwayDrug actionSMP00737
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 inhibitorNon-inhibitor0.8707
CYP450 2D6 inhibitorNon-inhibitor0.7852
CYP450 2C19 inhibitorNon-inhibitor0.8667
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral300 mg/1
Tablet, film coatedoral300 mg/1
Tabletoral
Tablet, film coatedoral
Solutionoral20 mg/mL
Solutionoral20 mg
Tabletoral300 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
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1340589 No1999-06-082016-06-08Canada
CA2216634 No2004-07-202016-03-28Canada
CA2289753 No2007-01-232018-05-14Canada
US5089500 No1992-12-262009-12-26Us
US5905082 Yes1996-11-182016-11-18Us
US6294540 Yes1998-11-142018-11-14Us
US6417191 Yes1996-09-282016-09-28Us
US6641843 Yes1999-08-042019-08-04Us
US8129385 No2007-10-052027-10-05Us
US9242986 No2009-10-082029-10-08Us
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 References
  1. Zucman D, Truchis Pd, 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:17356469 ]
  2. Link [Link]
External Links
ATC CodesJ05AF06J05AR02J05AR04J05AR13
AHFS Codes
  • 08:18.08.20
PDB EntriesNot Available
FDA labelDownload (118 KB)
MSDSDownload (34.7 KB)
Interactions
Drug Interactions
Drug
AtazanavirThe serum concentration of Abacavir can be decreased when it is combined with Atazanavir.
BatimastatThe serum concentration of Abacavir can be decreased when it is combined with Batimastat.
DarunavirThe serum concentration of Abacavir can be decreased when it is combined with Darunavir.
FosamprenavirThe serum concentration of Abacavir can be decreased when it is combined with Fosamprenavir.
GanciclovirThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Abacavir.
IndinavirThe serum concentration of Abacavir can be decreased when it is combined with Indinavir.
IsoflurophateThe serum concentration of Abacavir can be decreased when it is combined with Isoflurophate.
MethadoneThe therapeutic efficacy of Abacavir can be decreased when used in combination with Methadone.
NelfinavirThe serum concentration of Abacavir can be decreased when it is combined with Nelfinavir.
RibavirinRibavirin may increase the hepatotoxic activities of Abacavir.
RitonavirThe serum concentration of Abacavir can be decreased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Abacavir can be decreased when it is combined with Saquinavir.
SimeprevirThe serum concentration of Abacavir can be decreased when it is combined with Simeprevir.
TipranavirThe serum concentration of Abacavir can be decreased when it is combined with Tipranavir.
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

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
yes
Actions
inhibitor
General Function:
Rna-dna hybrid ribonuclease activity
Specific Function:
Not Available
Gene Name:
pol
Uniprot ID:
Q72547
Molecular Weight:
65223.615 Da
References
  1. De Clercq E: New anti-HIV agents and targets. Med Res Rev. 2002 Nov;22(6):531-65. [PubMed:12369088 ]
  2. 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:9145876 ]
  3. 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:11667311 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Zinc ion binding
Specific Function:
Not Available
Gene Name:
ADH6
Uniprot ID:
P28332
Molecular Weight:
39088.335 Da
References
  1. Yuen GJ, Weller S, Pakes GE: A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351-71. [PubMed:18479171 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid binding
Specific Function:
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. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naph...
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da
References
  1. Yuen GJ, Weller S, Pakes GE: A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351-71. [PubMed:18479171 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Poly(a) rna binding
Specific Function:
ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.
Gene Name:
ADK
Uniprot ID:
P55263
Molecular Weight:
40545.075 Da
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:9145876 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on May 24, 2016 03:10