U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H19F2N3O5
Molecular Weight 419.3795
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DOLUTEGRAVIR

SMILES

C[C@]1([H])CCO[C@@]2([H])Cn3cc(c(=O)c(c3C(=O)N12)O)C(=NCc4ccc(cc4F)F)O

InChI

InChIKey=RHWKPHLQXYSBKR-BMIGLBTASA-N
InChI=1S/C20H19F2N3O5/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)/t10-,15+/m1/s1

HIDE SMILES / InChI

Molecular Formula C20H19F2N3O5
Molecular Weight 419.3795
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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

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

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.70000000000000018 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1376265600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.67 μg/mL
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
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
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
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
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
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%
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%
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:
healthy, 33.5 years (range 24–63 years)
Health Status: healthy
Age Group: 33.5 years (range 24–63 years)
Sex: M+F
Sources:
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
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:
AEs

AEs

AESignificanceDosePopulation
Diarrhea 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
Dizziness 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
Oropharyngeal pain 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
Viral infection 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
Vomiting 2%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
Nausea 20%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
Abdominal pain 5%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
Headache 7%
250 mg single, oral
Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
healthy, 34.5 ± 10.5 years
Health Status: healthy
Age Group: 34.5 ± 10.5 years
Sex: M+F
Sources:
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
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

Sample Use Guides

The recommended dose is 50 mg once daily or twice daily depending on therapy.
Route of Administration: Oral
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
Substance Class Chemical
Created
by admin
on Sat Jun 26 04:12:09 UTC 2021
Edited
by admin
on Sat Jun 26 04:12:09 UTC 2021
Record UNII
DKO1W9H7M1
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DOLUTEGRAVIR
DASH   INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
S-349572
Code English
DOLUTEGRAVIR [INN]
Common Name English
GSK1349572A
Code English
DTG
Common Name English
DOLUTEGRAVIR [WHO-DD]
Common Name English
DOLUTEGRAVIR [USAN]
Common Name English
GSK1349572
Code English
GSK-1349572
Code English
DOLUTEGRAVIR [VANDF]
Common Name English
DOLUTEGRAVIR [MI]
Common Name English
GSK 1349572
Code English
(4R,12.ALPHA.S)-N-((2,4-DIFLUOROPHENYL)METHYL)-7-HYDROXY-4-METHYL-6,8-DIOXO-3,4,6,8,12,12.ALPHA.-HEXAHYDRO-2H-PYRIDO(1',2':4,5)PYRAZINO(2,1-.BETA.)(1,3)OXAZINE-9-CARBOXAMIDE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C281
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
WHO-ATC J05AR13
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
NDF-RT N0000175887
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
WHO-VATC QJ05AX12
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
WHO-ATC J05AR21
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
WHO-ATC J05AX12
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
Code System Code Type Description
LACTMED
Dolutegravir
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
NCI_THESAURUS
C121543
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
DRUG CENTRAL
4805
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
HSDB
8152
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
ChEMBL
CHEMBL1229211
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
DRUG BANK
DB08930
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
CAS
1051375-16-6
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
PUBCHEM
54726191
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
EVMPD
SUB35122
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
INN
9261
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
RXCUI
1433868
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY RxNorm
MESH
C562325
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
MERCK INDEX
M4730
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY Merck Index
NDF-RT
N0000187061
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY Organic Cation Transporter 2 Inhibitors [MoA]
FDA UNII
DKO1W9H7M1
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
WIKIPEDIA
DOLUTEGRAVIR
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
NDF-RT
N0000191423
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY Multidrug and Toxin Extrusion Transporter 1 Inhibitors [MoA]
IUPHAR
7365
Created by admin on Sat Jun 26 04:12:10 UTC 2021 , Edited by admin on Sat Jun 26 04:12:10 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET ORGANISM->INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MINOR
EXCRETED UNCHANGED
URINE
TRANSPORTER -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
MINOR
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC HIGH-FAT MEAL

ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

FASTED STATE

Volume of Distribution PHARMACOKINETIC ONCE DAILY ADMINISTRATION