Bictegravir

Identification

Summary

Bictegravir is an integrase inhibitor used to treat HIV infections.

Brand Names

Biktarvy

Generic Name

Bictegravir

DrugBank Accession Number

DB11799

Background

Bictegravir is a recently approved investigational drug that has been used in trials studying the treatment of HIV-1 and HIV-2 infection. It has been approved for HIV-1 monotherapy combined with 2 other antiretrovirals in a single tablet.⁷

Type

Small Molecule

Groups

Approved, Investigational

Structure

Similar Structures

Weight: Average: 449.386
Monoisotopic: 449.119855181
Chemical Formula: C₂₁H₁₈F₃N₃O₅

Synonyms

Bictegravir

External IDs

GS-9883
GS-9883-01

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Pharmacology

Indication

Bictegravir is indicated in the management of HIV-1 infection in patients not previously treated with antiretroviral therapy. Additionally, Bictegravir is indicated in the management of HIV-1 infection in patients who are virologically suppressed (HIV-1 RNA <50 c/mL) on a regular antiretroviral regimen for a minimum of three months without a history of failure in treatment and no known factors associated with the resistance to the individual components of the medication. It is used in combination with tenofovir and emtricitabine.^3,4,8

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used in combination to treat	Human immunodeficiency virus type 1 (hiv-1) infection	Combination Product in combination with: Emtricitabine (DB00879), Tenofovir alafenamide (DB09299)	••••••••••••		••••••••••••• •••••••••• •••••• ••• •••• •••• •• •••••• ••• •••• •••••• •• ••••• •• ••• •• ••••••• •• ••••••••• •••••••• •••••• •••••••••••••• •••••••	••••••
Used in combination to treat	Human immunodeficiency virus type 1 (hiv-1) infection	Combination Product in combination with: Tenofovir alafenamide (DB09299), Emtricitabine (DB00879)	••••••••••••	•••••• •••••••••	•••••• •• ••••• •• ••• •••••••••••••• ••••••••• •••••	••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

Bictegravir is an HIV-1 integrase strand transfer inhibitor (INSTI). Bictegravir (BIC) inhibits HIV-1 virus replication into the human genome. It can be taken once daily without additional dosing ^2,3,4,5. Bictegravir (BIC) inhibits strand transfer of viral DNA into the host genome and thereby prevents HIV-1 replication ⁵.

Mechanism of action

This single dose medication inhibits the strand transfer of viral DNA into the human genome, preventing HIV-1 virus replication and propagation ².

In vitro, bictegravir has shown powerful antiviral activity against HIV-2 and various subtypes of HIV-1. It has shown synergistic effects when combined with other ARVs, including tenofovir alafenamide (TAF), emtricitabine (FTC), and darunavir (DRV). The three components of the first USA approved medication ( trade name: Biktarvy ) are as follows:

Bictegravir: integrase strand transfer inhibitor; INSTI), an HIV-1 encoded enzyme necessary for viral replication. Inhibition of the integrase enzyme prevents the integration of HIV-1 into host DNA, blocking the conversion of the HIV-1 provirus and progression of the virus ^Label.

Emtricitabine: FTC, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine is phosphorylated to form emtricitabine 5'-triphosphate intracellularly. This metabolite inhibits the activity of human immunodeficiency virus (HIV) reverse transcriptase by competing with the substrate deoxycytidine 5'-triphosphate and by incorporating itself into viral DNA preventing DNA chain elongation ^Label.

Tenofovir Alafenamide: TAF is a phosphonamidate prodrug of tenofovir (2′-deoxyadenosine monophosphate analog). Plasma exposure to TAF leads to leakage into cells and then TAF is intracellularly converted to tenofovir by hydrolysis by cathepsin. Tenofovir is subsequently phosphorylated by cellular kinases to the metabolite tenofovir diphosphate, which is the active form of the drug. Tenofovir diphosphate inhibits HIV-1 replication by incorporating into viral DNA by the HIV reverse transcriptase, resulting in DNA chain-termination. Tenofovir diphosphate also weakly inhibits mammalian DNA polymerases ^Label.

Target	Actions	Organism
AReverse transcriptase/RNaseH	antagonist	Human immunodeficiency virus 1
AIntegrase	antagonist	Human immunodeficiency virus 1

Absorption

Bictegravir is rapidly absorbed within the body. Tmax= 2.0-4.0h ³

Volume of distribution

0.2 L/Kg in humans ²

Protein binding

> 99 % bound to human plasma Blood to plasma ratio: 0.64 ²

Metabolism

In a 10-day dose-ranging study, monotherapy (5 mg to 100 mg) once daily in adults who were not previously treated with bictegravir, the median half-life of BIC ranged from 15.9 h - 20.9 h ³. Bictegravir is metabolized in the liver and kidneys. CYP3A4 and UGT1A are the primary enzymes involved in the metabolism of bictegravir. Administration of bictegravir is not advised in patients with renal creatinine clearance of <30 mL/min and patients with hepatic disease ^Label.

Route of elimination

BIC is mainly eliminated through UGT1A1 glucuronidation and CYP3A4 oxidation, equally ². About 1% of the bictegravir dose is excreted in the urine, unchanged ^2,3.

Half-life

Half-life is 17.3 hours.⁶

Clearance

Bictegravir is mainly cleared by the kidneys. Those with renal clearance <30 should not take bictegravir ^Label

Adverse Effects

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Toxicity

Those with renal disease and creatinine clearance of <30 mL/min should not take bictegravir ^Label. Patients with hepatic disease should not take bictegravir.

Most common adverse reactions include diarrhea, nausea, and headache ^Label.

Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms/laboratory findings suggesting lactic acidosis or hepatotoxicity.

Pathways

Not Available

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Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abametapir	The serum concentration of Bictegravir can be increased when it is combined with Abametapir.
Abemaciclib	The excretion of Abemaciclib can be decreased when combined with Bictegravir.
Acyclovir	The excretion of Acyclovir can be decreased when combined with Bictegravir.
Adenine	The metabolism of Bictegravir can be decreased when combined with Adenine.
Adenovirus type 7 vaccine live	The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Bictegravir.

Food Interactions

Avoid St. John's Wort.
Take at the same time every day.
Take separate from antacids. Take bictegravir at least 2 hours before or 6 hours after taking antacids containing aluminum or magnesium.
Take with food. When taking iron or calcium-containing products, bictegravir should be taken with food.
Take with or without food.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Bictegravir sodium	4L5MP1Y7W7	1807988-02-8	WJNFBIVCQMPPJC-FQYDJHLKSA-M

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Biktarvy	Bictegravir sodium (30 mg/1) + Emtricitabine (120 mg/1) + Tenofovir alafenamide fumarate (15 mg/1)	Tablet	Oral	Gilead Sciences, Inc.	2021-10-07	Not applicable
Biktarvy	Bictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg)	Tablet, film coated	Oral	Gilead Sciences Ireland Uc	2021-06-01	Not applicable
Biktarvy	Bictegravir sodium (50 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (25 mg/1)	Tablet	Oral	Gilead Sciences, Inc.	2018-02-07	Not applicable
Biktarvy	Bictegravir sodium (50 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide fumarate (25 mg)	Tablet, film coated	Oral	Gilead Sciences Ireland Uc	2020-12-15	Not applicable
BIKTARVY	Bictegravir (50 MG) + Emtricitabine (200 MG) + Tenofovir alafenamide (25 MG)	Tablet, film coated	Oral	Gilead Sciences Ireland Uc	2019-01-29	Not applicable

Chemical Identifiers

UNII: 8GB79LOJ07
CAS number: 1611493-60-7
InChI Key: SOLUWJRYJLAZCX-LYOVBCGYSA-N
InChI: 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
IUPAC Name: (1S,11R,13R)-5-hydroxy-3,6-dioxo-N-[(2,4,6-trifluorophenyl)methyl]-12-oxa-2,9-diazatetracyclo[11.2.1.0^{2,11}.0^{4,9}]hexadeca-4,7-diene-7-carboxamide
SMILES: OC1=C2N(C[C@H]3O[C@@H]4CC[C@@H](C4)N3C2=O)C=C(C(=O)NCC2=C(F)C=C(F)C=C2F)C1=O

References

General References

Chase SP, Freimanis AK: Abdominal echography. Ohio State Med J. 1971 Oct;67(10):901-6. [Article]
Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1–Infected Adults [Link]
BICTEGRAVIR [Link]
FDA APPROVES BIKTARVY [Link]
BICTEGRAVIR SODIUM [Link]
FDA Approved Drug Products: BIKTARVY (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use [Link]
FDA Approved Drug Products: BIKTARVY (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use (October 2022) [Link]
EMA Approved Drug Products: Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) Oral Tablets [Link]

External Links

PubChem Compound: 90311989
PubChem Substance: 347828148
ChemSpider: 44208822
BindingDB: 330048
RxNav: 1999660
ChEBI: 172943
ChEMBL: CHEMBL3989866
PDBe Ligand: KLQ
Wikipedia: Bictegravir

PDB Entries

6puw / 6rwm / 6rwo / 7ouh

FDA label

Download (720 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Health Services Research	Human Immunodeficiency Virus (HIV) Infections	1
4	Active Not Recruiting	Treatment	Acute HIV Infection	1
4	Active Not Recruiting	Treatment	Drug Use / Human Immunodeficiency Virus (HIV) Infections / Reduction, Harm	1
4	Active Not Recruiting	Treatment	HIV-infected Patient Kidney Transplant Recipient	1
4	Active Not Recruiting	Treatment	Human Immunodeficiency Virus (HIV) Infections	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral
Tablet, coated	Oral
Tablet, film coated	Oral

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US6642245	Yes	2003-11-04	2021-05-04
US6703396	Yes	2004-03-09	2021-09-09
US9296769	Yes	2016-03-29	2033-02-15
US7803788	No	2010-09-28	2022-02-02
US8754065	Yes	2014-06-17	2033-02-15
US7390791	Yes	2008-06-24	2025-10-17
US9216996	No	2015-12-22	2033-12-19
US9708342	No	2017-07-18	2035-06-19
US9732092	No	2017-08-15	2033-12-19
US10385067	No	2019-08-20	2035-06-19
US10548846	No	2020-02-04	2036-11-08
US11744802	No	2016-11-08	2036-11-08

Properties

State

Solid

Experimental Properties

Property	Value	Source
boiling point (°C)	682.5±55.0 °C at 760 mmHg	[L1221]

Predicted Properties

Property	Value	Source
Water Solubility	0.0537 mg/mL	ALOGPS
logP	1.28	ALOGPS
logP	1.36	Chemaxon
logS	-3.9	ALOGPS
pKa (Strongest Acidic)	9.81	Chemaxon
pKa (Strongest Basic)	-0.3	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	6	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	99.18 Å²	Chemaxon
Rotatable Bond Count	3	Chemaxon
Refractivity	105.44 m³·mol^-1	Chemaxon
Polarizability	41.14 Å³	Chemaxon
Number of Rings	5	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-0090000000-f7664c9a47d6001aa621
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0002-0033900000-3261c687e9a3ce0a6042
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-000l-0190100000-31cb555762b0823317fe
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03mj-0131900000-c811dd4a24fca6977230
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0fc0-0970100000-992dfacc024c47617ab9
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0a4i-1392400000-bda5c48565024141ed21
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	192.42169	predicted	DeepCCS 1.0 (2019)
[M+H]+	194.81728	predicted	DeepCCS 1.0 (2019)
[M+Na]+	200.72978	predicted	DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.

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Details1. Reverse transcriptase/RNaseH

Kind: Protein
Organism: Human immunodeficiency virus 1
Pharmacological action: Yes
Actions: Antagonist

General Function: Rna-dna hybrid ribonuclease activity
Specific Function: Not Available
Gene Name: pol
Uniprot ID: Q72547
Uniprot Name: Reverse transcriptase/RNaseH
Molecular Weight: 65223.615 Da

Details2. Integrase

Kind: Protein
Organism: Human immunodeficiency virus 1
Pharmacological action: Yes
Actions: Antagonist

General Function: Zinc ion binding
Specific Function: Not Available
Gene Name: pol
Uniprot ID: Q7ZJM1
Uniprot Name: Integrase
Molecular Weight: 32226.645 Da

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

Details2. UDP-glucuronosyltransferase 1-1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid binding
Specific Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name: UGT1A1
Uniprot ID: P22309
Uniprot Name: UDP-glucuronosyltransferase 1-1
Molecular Weight: 59590.91 Da

Details3. POU domain, class 2, transcription factor 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function: Transcription factor that specifically binds to the octamer motif (5'-ATTTGCAT-3'). Regulates transcription in a number of tissues in addition to activating immunoglobulin gene expression. Modulate...
Gene Name: POU2F2
Uniprot ID: P09086
Uniprot Name: POU domain, class 2, transcription factor 2
Molecular Weight: 51208.51 Da

Details4. Multidrug and toxin extrusion protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Monovalent cation:proton antiporter activity
Specific Function: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name: SLC47A1
Uniprot ID: Q96FL8
Uniprot Name: Multidrug and toxin extrusion protein 1
Molecular Weight: 61921.585 Da

References

Biktarvy FDA label [File]

Drug created at October 20, 2016 20:49 / Updated at December 06, 2022 13:40

Bictegravir

Identification

Structure for Bictegravir (DB11799)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

Enzymes

References