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

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H18F3N3O5
Molecular Weight 449.3807
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BICTEGRAVIR

SMILES

C1C[C@]2([H])C[C@@]1([H])N3[C@@]([H])(Cn4cc(c(=O)c(c4C3=O)O)C(=NCc5c(cc(cc5F)F)F)O)O2

InChI

InChIKey=SOLUWJRYJLAZCX-LYOVBCGYSA-N
InChI=1S/C21H18F3N3O5/c22-9-3-14(23)12(15(24)4-9)6-25-20(30)13-7-26-8-16-27(10-1-2-11(5-10)32-16)21(31)17(26)19(29)18(13)28/h3-4,7,10-11,16,29H,1-2,5-6,8H2,(H,25,30)/t10-,11+,16+/m0/s1

HIDE SMILES / InChI

Molecular Formula C21H18F3N3O5
Molecular Weight 449.3807
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Bictegravir is a component of the fixed-dose combination product bictegravir/emtricitabine/tenofovir alafenamide (BIKTARVY®), which received marketing approval for the treatment of human immunodeficiency virus (HIV) infection by the U.S. Food and Drug Administration in February 2018. Bictegravir inhibits the strand transfer activity of HIV-1 integrase, an HIV-1 encoded enzyme that is required for viral replication. Inhibition of integrase prevents the integration of linear HIV-1 DNA into host genomic DNA, blocking the formation of the HIV-1 provirus and propagation of the virus.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BIKTARVY

Approved Use

BIKTARVY is a three-drug combination of bictegravir (BIC), a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI), and emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV-1 nucleoside analog reverse transcriptase inhibitors (NRTIs), and is indicated as a complete regimen for the treatment of HIV-1 infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 3 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of BIKTARVY.

Launch Date

1486339200000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
12235 ng/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
3475 ng/mL
25 mg 1 times / day steady-state, oral
dose: 25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
6080 ng/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
741.5 ng/mL
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
6.15 μg/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: EMTRICITABINE
BICTEGRAVIR SODIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
178901.7 ng × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
48950.3 ng × h/mL
25 mg 1 times / day steady-state, oral
dose: 25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
87538.4 ng × h/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9983 ng × h/mL
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
102 μg × h/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: EMTRICITABINE
BICTEGRAVIR SODIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
20.9 h
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
15.9 h
25 mg 1 times / day steady-state, oral
dose: 25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
17.8 h
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
20.8 h
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BICTEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
17.3 h
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: EMTRICITABINE
BICTEGRAVIR SODIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: EMTRICITABINE
BICTEGRAVIR SODIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Amylase, ALT...
Other AEs:
Amylase (grade 3-4, 2%)
ALT (grade 3-4, 1%)
Neutrophils (grade 3-4, 2%)
Sources:
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Diarrhea, Nausea...
Other AEs:
Diarrhea (all grades, 6%)
Nausea (all grades, 5%)
Headache (all grades, 5%)
Fatigue (all grades, 3%)
Abnormal dreams (all grades, 3%)
Dizziness (all grades, 2%)
Insomnia (all grades, 2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
ALT grade 3-4, 1%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Amylase grade 3-4, 2%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Neutrophils grade 3-4, 2%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Dizziness all grades, 2%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Insomnia all grades, 2%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Abnormal dreams all grades, 3%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Fatigue all grades, 3%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Headache all grades, 5%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Nausea all grades, 5%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Diarrhea all grades, 6%
50 mg 1 times / day multiple, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 176 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no
no
no
no
no
no
no
weak [IC50 >100 uM]
weak
yes [IC50 0.42 uM]
likely (co-administration study)
Comment: coadministration of BIKTARVY with drugs that are substrates of OCT2 may increase their plamsa concentrations
Page: 62, 66, 430
yes [IC50 8.04 uM]
likely (co-administration study)
Comment: coadministration of BIKTARVY with drugs that are substrates of MATE1 may increase their plamsa concentrations
Page: 62, 67, 430
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes (co-administration study)
Comment: rifampin decreased the mean bictegravir Cmax by 28% and AUC by 75%; rifbutin decreased the mean bictegravir Cmax by 20% and AUC by 38%
Page: 66, 67
yes
yes (co-administration study)
Comment: rifampin decreased the mean bictegravir Cmax by 28% and AUC by 75%; rifbutin decreased the mean bictegravir Cmax by 20% and AUC by 38%
Page: 66, 67
yes
yes (co-administration study)
Comment: rifampin decreased the mean bictegravir Cmax by 28% and AUC by 75%
Page: 66, 67
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile.
2016 Dec
Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1-Infected Adults.
2017 May 1
Bictegravir: First Global Approval.
2018 Apr
Patents

Patents

Sample Use Guides

BIKTARVY® is a three-drug fixed dose combination product containing 50 mg of bictegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide. The recommended dosage of BIKTARVY is one tablet taken orally once daily with or without food.
Route of Administration: Oral
The antiviral activity of bictegravir (BIC) against laboratory and clinical isolates of HIV-1 was assessed in lymphoblastoid cell lines, PBMCs, primary monocyte/macrophage cells, and CD4+ T-lymphocytes. In MT-4 cells (human lymphoblastoid T-cell line) acutely infected with HIV-1 IIIB, the mean 50% effective concentration (EC50) was 2.4+/-0.4 nM, and the protein-adjusted EC95 value was 361 nM (0.162 micrograms per mL). BIC displayed antiviral activity in activated PBMCs against clinical isolates of HIV-1 representing groups M, N, and O, including subtypes A, B, C, D, E, F, and G, with a median EC50 value of 0.55 nM (range <0.05 to 1.71 nM). The EC50 value against a single HIV-2 isolate was 1.1 nM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:13:52 UTC 2021
Edited
by admin
on Sat Jun 26 03:13:52 UTC 2021
Record UNII
8GB79LOJ07
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BICTEGRAVIR
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
BIKTARVY COMPONENT BICTEGRAVIR
Brand Name English
BICTEGRAVIR [MI]
Common Name English
BICTEGRAVIR [INN]
Common Name English
BICTEGRAVIR [USAN]
Common Name English
GS-9883
Code English
GS-9883-01
Code English
2,5-METHANOPYRIDO(1',2':4,5)PYRAZINO(2,1-B)(1,3)OXAZEPINE-10-CARBOXAMIDE, 2,3,4,5,7,9,13,13A-OCTAHYDRO-8-HYDROXY-7,9-DIOXO-N-((2,4,6-TRIFLUOROPHENYL)METHYL)-, (2R,5S,13AR)-
Systematic Name English
BICTEGRAVIR [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 559316
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
WHO-ATC J05AR20
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C171719
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
MERCK INDEX
M12125
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
PUBCHEM
90311989
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
DRUG CENTRAL
5274
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
FDA UNII
8GB79LOJ07
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
INN
10133
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
EVMPD
SUB182699
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
RXCUI
1999660
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
CAS
1611493-60-7
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
DRUG BANK
DB11799
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
LACTMED
Bictegravir
Created by admin on Sat Jun 26 03:13:53 UTC 2021 , Edited by admin on Sat Jun 26 03:13:53 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Coadministration of BIC (given without F/TAF) with rifampin decreased the mean BIC Cmax and AUC by 28% and 75%, respectively.
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
Co?administration of BIKTARVY with dofetilide may increase dofetilide plasma concentrations which can lead to serious and/or life threatening events.
IC50
BINDER->LIGAND
TARGET ORGANISM->INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
Co?administration of BIKTARVY with dofetilide may increase dofetilide plasma concentrations which can lead to serious and/or life threatening events.
CLINICALLY SIGNIFICANT
IC50
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
PLASMA; URINE
METABOLITE -> PARENT
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Cmax PHARMACOKINETIC ROUTE OF ADMINSTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC