ABACAVIR SUCCINATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H18N6O.C4H6O4
Molecular Weight	404.4204
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CCC(O)=O.NC1=NC2=C(N=CN2[C@@H]3C[C@H](CO)C=C3)C(NC4CC4)=N1

InChI

InChIKey=BOONDNCXQPMXQT-SCYNACPDSA-N

InChI=1S/C14H18N6O.C4H6O4/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;5-3(6)1-2-4(7)8/h1,4,7-10,21H,2-3,5-6H2,(H3,15,17,18,19);1-2H2,(H,5,6)(H,7,8)/t8-,10+;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C4H6O4
Molecular Weight	118.088
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C14H18N6O
Molecular Weight	286.3323
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24625462 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020977s032,020978s035lbl.pdf

Abacavir is a nucleoside reverse transcriptase inhibitor used for treatment of HIV infection (either alone or in combination with other antiviral drugs). It was shown that abacavir exerts its antiviral activity through its active metabolite, carbovir triphosphate. Carbovir triphosphate is a guanine analogue and a potent and selective inhibitor of viral reverse transcriptases. Upon administration, abacavir is first converted to abacavir monophosphate by ADK, then the monophosphate is deaminated to carbovir monophosphate, which is then anabolized by cellular kinases to carbovir diphosphate and then finally to carbovir triphosphate. Abacavir causes hypersensitivity reaction in patients with HLA-B*57:01 allele.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 reverse transcriptase 47 Target ID: CHEMBL247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24625462	Inhibitor 8228		21.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 150 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020977s032,020978s035lbl.pdf	Primary		Approved 8360	ZIAGEN Approved Use ZIAGEN, a nucleoside analogue human immunodeficiency virus (HIV-1) reverse transcriptase inhibitor, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Launch Date 9.1385279E11

C_max

Value	Dose	Co-administered	Analyte	Population
3 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020977s033s034,020978s036s037lbl.pdf	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ABACAVIR SULFATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
4.26 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020977s033s034,020978s036s037lbl.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		ABACAVIR SULFATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
6.02 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020977s033s034,020978s036s037lbl.pdf	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ABACAVIR SULFATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
11.95 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020977s033s034,020978s036s037lbl.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		ABACAVIR SULFATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.54 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020977s033s034,020978s036s037lbl.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		ABACAVIR SULFATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
50% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020977s033s034,020978s036s037lbl.pdf	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ABACAVIR SULFATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
150 mg single, intravenous Dose: 150 mg Route: intravenous Route: single Dose: 150 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10453964	unhealthy, 27–39 years n = 6 Health Status: unhealthy Condition: HIV-1-infection Age Group: 27–39 years Sex: M Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/10453964	Sources: https://pubmed.ncbi.nlm.nih.gov/10453964
1200 mg single, oral Highest studied dose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10049274	unhealthy, 38 years (range: 24–48 years) n = 12 Health Status: unhealthy Condition: HIV-1-infection Age Group: 38 years (range: 24–48 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10049274	Other AEs: Asthenia, Abdominal pain... Other AEs: Asthenia (33%) Abdominal pain (33%) Headache (25%) Diarrhea (17%) Dyspepsia (17%) Sources: https://pubmed.ncbi.nlm.nih.gov/10049274
600 mg 3 times / day steady, oral Highest studied dose Dose: 600 mg, 3 times / day Route: oral Route: steady Dose: 600 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10898676	unhealthy, > 13 years n = 20 Health Status: unhealthy Condition: HIV-1-infection Age Group: > 13 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/10898676	Sources: https://pubmed.ncbi.nlm.nih.gov/10898676
600 mg 1 times / day steady, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201107Orig1s000lbl.pdf	unhealthy n = 2670 Health Status: unhealthy Condition: HIV infection Population Size: 2670 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201107Orig1s000lbl.pdf	Other AEs: Hypersensitivity reaction... Other AEs: Hypersensitivity reaction (serious\|grade 5, 8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201107Orig1s000lbl.pdf

AEs

AE	Significance	Dose	Population
Diarrhea	17%	1200 mg single, oral Highest studied dose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10049274	unhealthy, 38 years (range: 24–48 years) n = 12 Health Status: unhealthy Condition: HIV-1-infection Age Group: 38 years (range: 24–48 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10049274
Dyspepsia	17%	1200 mg single, oral Highest studied dose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10049274	unhealthy, 38 years (range: 24–48 years) n = 12 Health Status: unhealthy Condition: HIV-1-infection Age Group: 38 years (range: 24–48 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10049274
Headache	25%	1200 mg single, oral Highest studied dose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10049274	unhealthy, 38 years (range: 24–48 years) n = 12 Health Status: unhealthy Condition: HIV-1-infection Age Group: 38 years (range: 24–48 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10049274
Abdominal pain	33%	1200 mg single, oral Highest studied dose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10049274	unhealthy, 38 years (range: 24–48 years) n = 12 Health Status: unhealthy Condition: HIV-1-infection Age Group: 38 years (range: 24–48 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10049274
Asthenia	33%	1200 mg single, oral Highest studied dose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10049274	unhealthy, 38 years (range: 24–48 years) n = 12 Health Status: unhealthy Condition: HIV-1-infection Age Group: 38 years (range: 24–48 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10049274
Hypersensitivity reaction	serious\|grade 5, 8%	600 mg 1 times / day steady, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201107Orig1s000lbl.pdf	unhealthy n = 2670 Health Status: unhealthy Condition: HIV infection Population Size: 2670 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201107Orig1s000lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:421707	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:421707
ChemicalBook	CB5698138	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5698138
MolPort	MolPort-006-069-118	https://www.molport.com/shop/molecule-link/MolPort-006-069-118
ZINC	ZINC000002015928	http://zinc15.docking.org/substances/ZINC000002015928
eMolecules	30512521	https://www.emolecules.com/cgi-bin/more?vid=30512521

PubMed

Title	Date	PubMed
Abacavir and mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase, have profound and synergistic anti-HIV activity.	1999 Aug 15	10458616
Hydroxyurea-induced neurotoxicity in HIV disease.	1999 Aug 20	10465092
A novel genotype encoding a single amino acid insertion and five other substitutions between residues 64 and 74 of the HIV-1 reverse transcriptase confers high-level cross-resistance to nucleoside reverse transcriptase inhibitors. Abacavir CNA2007 International Study Group.	1999 Oct 1	10843527
Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy.	2000 Dec 15	11141242
An open-label randomized trial to evaluate different therapeutic strategies of combination therapy in HIV-1 infection: design, rationale, and methods of the initio trial.	2001 Apr	11306154
A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection.	2001 Apr 15	11391161
[Observational study with abacavir. Decreased viral load and quality of life improves].	2001 Apr 2	11373782
Antiviral activity of tenofovir (PMPA) against nucleoside-resistant clinical HIV samples.	2001 Apr-Jul	11562951
Strategies for treating HIV-related lipodystrophy.	2001 Aug	11772261
Antiviral drugs: current state of the art.	2001 Aug	11418355
Understanding drug hypersensitivity: what to look for when prescribing abacavir.	2001 Dec	11806176
Agranulocytosis and fever seven weeks after starting abacavir.	2001 Dec 7	11774836
Trizivir on the market.	2001 Jan	11166234
Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-1-infected patients with failure of highly active antiretroviral therapy.	2001 Jan 1	11176267
Abacavir and diabetes.	2001 Jan 11	11188420
The abacavir hypersensitivity reaction and interruptions in therapy.	2001 Jul 6	11426085
Increased turnover of CCR5+ and redistribution of CCR5- CD4 T lymphocytes during primary human immunodeficiency virus type 1 infection.	2001 Mar 1	11181150
Resistant to everything.	2001 May	11682786
Drifting agenda for federal treatment research.	2001 May	11548299
Choosing which nuke to use first.	2001 May	11392690
New developments in anti-HIV chemotherapy.	2001 Nov	11562282
Lipodystrophy in HIV-1-positive patients is associated with insulin resistance in multiple metabolic pathways.	2001 Nov 9	11684928
Abacavir sulfate, lamivudine, and zidovudine (Trizivir).	2001 Nov-Dec	11723917
Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir.	2001 Oct	11726000
Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study.	2001 Oct 20	11684213
Improvement of HAART-associated insulin resistance and dyslipidemia after replacement of protease inhibitors with abacavir.	2001 Oct 29	11698228
Genotypic resistance mutations to antiretroviral drugs in HIV-1 B and non-B subtypes from Cuba.	2001 Sep	11702373
Pharmacokinetics of abacavir in HIV-1-infected patients with impaired renal function.	2001 Sep	11528234
Comparison of genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine.	2001 Sep 15	11517441
Broad nucleoside-analogue resistance implications for human immunodeficiency virus type 1 reverse-transcriptase mutations at codons 44 and 118.	2002 Apr 1	11920313
Abacavir hypersensitivity reaction.	2002 Apr 15	11915004
Efficacy of highly active antiretroviral therapy in HIV-1 infected children.	2002 Feb	11901656
Easier abacavir regimen has promising results.	2002 Jan	11862734
Vertigo and abacavir.	2002 Jan	11839213
Antiretroviral rounds. A very discordant response.	2002 Jan	11802628
Combined effect of zidovudine (ZDV), lamivudine (3TC) and abacavir (ABC) antiretroviral therapy in suppressing in vitro FIV replication.	2002 Jan	11684314
Kawasaki-like syndrome: abacavir hypersensitivity?	2002 Jan 1	11731962
Evidence of immune reconstitution in antiretroviral drug-experienced patients with advanced HIV disease.	2002 Jan 20	11839142
Novel use of a guanosine prodrug approach to convert 2',3'-didehydro-2',3'-dideoxyguanosine into a viable antiviral agent.	2002 Mar	11850281
Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with other nucleoside reverse transcriptase inhibitors.	2002 Mar	11850253
Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with and without nelfinavir in children with HIV-1 who have not previously been treated: the PENTA 5 randomised trial.	2002 Mar 2	11888583
Individualising HIV treatment--pharmacogenetics and immunogenetics.	2002 Mar 2	11888578

Patents

Sample Use Guides

In Vivo Use Guide

Adults: 600 mg daily, administered as either 300 mg twice daily or 600 mg once daily. Pediatric Patients Aged 3 Months and Older: Administered either once or twice daily. Dose should be calculated on body weight (kg) and should not exceed 600 mg daily.

Route of Administration: Oral

In Vitro Use Guide

In order to study the inhibitory effect of abacavir on HIV strains, MT-2 cell line was infected with HIV-1 strain IIIB and was treated with increasing concentrations of the drug (up to 100 uM).

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:21:46 UTC 2023` Edited by `admin` on `Wed Jul 05 23:21:46 UTC 2023`
Record UNII	40FH6D8CHK
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ABACAVIR SUCCINATE

Official Name

English

2-CYCLOPENTENE-1-METHANOL, 4-(2-AMINO-6-(CYCLOPROPYLAMINO)-9H-PURIN-9-YL)-, (1S-CIS)-, BUTANEDIOATE (1:1) (SALT)

Common Name

English

(1S,4R)-4-(2-AMINO-6(CYCLOPROPYLAMINO)-9H-PURIN-9-YL)-2-CYCLOPENTENE-1-METHANOL SUCCINATE(1:1) (SALT)

Common Name

English

ABACAVIR SUCCINATE [USAN]

Common Name

English

Abacavir succinate [WHO-DD]

Common Name

English

ABACAVIR SUCCINATE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C97452