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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H18F2N3O5.Na.H2O
Molecular Weight 459.3759
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DOLUTEGRAVIR SODIUM MONOHYDRATE

SMILES

O.[Na+].[H][C@]12CN3C=C(C(=O)NCC4=CC=C(F)C=C4F)C(=O)C([O-])=C3C(=O)N1[C@H](C)CCO2

InChI

InChIKey=UDYLZWGOPQBQQT-ZSYJTXGQSA-M
InChI=1S/C20H19F2N3O5.Na.H2O/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22;;/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28);;1H2/q;+1;/p-1/t10-,15+;;/m1../s1

HIDE SMILES / InChI

Description

Dolutegravir is an integrase inhibitor that is meant to be used as part of combination therapy for the treatment of HIV. Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. Dolutegravir coadministered with dofetilide can result in potentially life-threatening adverse events.

CNS Activity

CNS Penetrant
2554
Curator's Comment: Although dolutegravir appears to cross the blood–brain barrier, clinical outcomes have not been determined.

Originator

Approval Year

2013
596
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 2.7 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
TIVICAY

Approved Use

Indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 30 kg.

Launch Date

2013
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.67 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOLUTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.15 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
[NO STEREO] DOLUTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
53.6 μg × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOLUTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
75.1 μg × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
[NO STEREO] DOLUTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOLUTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
14 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
[NO STEREO] DOLUTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.1%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOLUTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.1%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
[NO STEREO] DOLUTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
50 mg 1 times / day steady, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30272231
healthy, 33.5 years (range 24–63 years)
n = 11
Health Status: healthy
Age Group: 33.5 years (range 24–63 years)
Sex: M+F
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/30272231
Sources:
https://pubmed.ncbi.nlm.nih.gov/30272231
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Other AEs: Nausea, Headache...
Other AEs:
Nausea (20%)
Headache (7%)
Abdominal pain (5%)
Diarrhea (2%)
Dizziness (2%)
Oropharyngeal pain (2%)
Vomiting (2%)
Viral infection (2%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
AEs

AEs

AESignificanceDosePopulation
Diarrhea 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Dizziness 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Oropharyngeal pain 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Viral infection 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Vomiting 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Nausea 20%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Abdominal pain 5%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Headache 7%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
healthy, 34.5 ± 10.5 years
n = 41
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Population Size: 41
Sources:
https://pubmed.ncbi.nlm.nih.gov/22422361
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:76010
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:76010
ChemicalBook
CB62538916
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62538916
MolPort
MolPort-023-293-507
https://www.molport.com/shop/molecule-link/MolPort-023-293-507
Selleck Chemicals
s-gsk1349572
http://www.selleckchem.com/products/s-gsk1349572.html
ZINC
ZINC000058581064
http://zinc15.docking.org/substances/ZINC000058581064
PubMed

PubMed

TitleDatePubMed
Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers.
2010 Jan
S/GSK1349572, a new integrase inhibitor for the treatment of HIV: promises and challenges.
2011 Apr
Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572).
2011 Oct
Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults.
2011 Sep 10
Dolutegravir for the treatment of HIV.
2012 Apr
The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults.
2012 Nov 1
Antiretroviral therapy: dolutegravir sets SAIL(ING).
2013 Aug 24
Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study.
2013 Aug 24
In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor.
2013 Feb
Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness.
2013 Jun
Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir.
2013 Nov
Dolutegravir: first global approval.
2013 Sep
Dolutegravir (Tivicay) for HIV.
2013 Sep 30
Patents

Patents

20090318421
5
20110190236
3
20120115875
5

Sample Use Guides

In Vivo Use Guide
The recommended dose is 50 mg once daily or twice daily depending on therapy.
Route of Administration: Oral
In Vitro Use Guide
Dolutegravir exhibited antiviral activity against laboratory strains of wild-type HIV-1 with mean EC50 values of 0.5 nM (0.21 ng/mL) to 2.1 nM (0.85 ng/mL) in peripheral blood mononuclear cells (PBMCs) and MT-4 cells. Dolutegravir exhibited antiviral activity against 13 clinically diverse clade B isolates with a mean EC50 value of 0.52 nM in a viral integrase susceptibility assay using the integrase coding region from clinical isolates. Dolutegravir demonstrated antiviral activity in cell culture against a panel of HIV-1 clinical isolates (3 in each group of M clades A, B, C, D, E, F, and G, and 3 in group O) with EC50 values ranging from 0.02 nM to 2.14 nM for HIV-1. Dolutegravir EC50 values against 3 HIV-2 clinical isolates in PBMC assays ranged from 0.09 nM to 0.61 nM.
Name Type Language
DOLUTEGRAVIR SODIUM MONOHYDRATE
Common Name English
GSK-1349572A HYDRATE
Code English
2H-PYRIDO(1',2':4,5)PYRAZINO(2,1-B)(1,3)OXAZINE-9-CARBOXAMIDE, N-((2,4-DIFLUOROPHENYL)METHYL)-3,4,6,8,12,12A-HEXAHYDRO-7-HYDROXY-4-METHYL-6,8-DIOXO-, SODIUM SALT, HYDRATE (1:1:1), (4R,12AS)-
Common Name English
Code System Code Type Description
CAS
1229006-39-6
Created by admin on Fri Dec 15 19:13:48 GMT 2023 , Edited by admin on Fri Dec 15 19:13:48 GMT 2023
PRIMARY
FDA UNII
0E1T06685X
Created by admin on Fri Dec 15 19:13:48 GMT 2023 , Edited by admin on Fri Dec 15 19:13:48 GMT 2023
PRIMARY
EPA CompTox
DTXSID80153785
Created by admin on Fri Dec 15 19:13:48 GMT 2023 , Edited by admin on Fri Dec 15 19:13:48 GMT 2023
PRIMARY
PUBCHEM
76969888
Created by admin on Fri Dec 15 19:13:48 GMT 2023 , Edited by admin on Fri Dec 15 19:13:48 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of DOLUTEGRAVIR
NIH
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