Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H18F2N3O5.Na |
Molecular Weight | 441.3606 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[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=UGWJRRXTMKRYNK-VSLILLSYSA-M
InChI=1S/C20H19F2N3O5.Na/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);/q;+1/p-1/t10-,15+;/m1./s1
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
Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598225/
Curator's Comment: Although dolutegravir appears to cross the blood–brain barrier, clinical outcomes have not been determined.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3471 |
2.7 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | TIVICAY Approved UseIndicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 30 kg. Launch Date2013 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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) n = 11 Health Status: healthy Age Group: 33.5 years (range 24–63 years) Sex: M+F Population Size: 11 Sources: |
|
250 mg single, oral Studied dose |
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: |
Other AEs: Nausea, Headache... Other AEs: Nausea (20%) Sources: Headache (7%) Abdominal pain (5%) Diarrhea (2%) Dizziness (2%) Oropharyngeal pain (2%) Vomiting (2%) Viral infection (2%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diarrhea | 2% | 250 mg single, oral Studied dose |
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: |
Dizziness | 2% | 250 mg single, oral Studied dose |
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: |
Oropharyngeal pain | 2% | 250 mg single, oral Studied dose |
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: |
Viral infection | 2% | 250 mg single, oral Studied dose |
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: |
Vomiting | 2% | 250 mg single, oral Studied dose |
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: |
Nausea | 20% | 250 mg single, oral Studied dose |
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: |
Abdominal pain | 5% | 250 mg single, oral Studied dose |
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: |
Headache | 7% | 250 mg single, oral Studied dose |
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: |
PubMed
Title | Date | PubMed |
---|---|---|
Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. | 2010 Jan |
|
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 |
|
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 |
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
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 | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Brand Name | English | ||
|
Brand Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Code | English | ||
|
Brand Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C281
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
||
|
EMA ASSESSMENT REPORTS |
TIVICAY (AUTHORIZED: HIV INFECTIONS)
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
46216142
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
1Q1V9V5WYQ
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
m4730
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | Merck Index | ||
|
WW-51
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
C148408
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
76007
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
1433867
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | RxNorm | ||
|
DTXSID201027849
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
CHEMBL1229211
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
100000156669
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
DBSALT000943
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
1051375-19-9
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
1Q1V9V5WYQ
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY | |||
|
SUB130591
Created by
admin on Fri Dec 15 18:45:27 GMT 2023 , Edited by admin on Fri Dec 15 18:45:27 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
SUBSTANCE RECORD