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

Details

Stereochemistry ACHIRAL
Molecular Formula C20H20FN6O5.K
Molecular Weight 482.5075
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RALTEGRAVIR POTASSIUM

SMILES

Cc1nnc(C(=O)NC(C)(C)c2nc(c(c(=O)n2C)[O-])C(=NCc3ccc(cc3)F)O)o1.[K+]

InChI

InChIKey=IFUKBHBISRAZTF-UHFFFAOYSA-M
InChI=1S/C20H21FN6O5.K/c1-10-25-26-17(32-10)16(30)24-20(2,3)19-23-13(14(28)18(31)27(19)4)15(29)22-9-11-5-7-12(21)8-6-11;/h5-8,28H,9H2,1-4H3,(H,22,29)(H,24,30);/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula C20H20FN6O5
Molecular Weight 443.4092
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula K
Molecular Weight 39.0983
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Raltegravir (RAL, Isentress, formerly MK-0518) is an antiretroviral drug produced by Merck & Co., used to treat HIV and it is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in patients 4 weeks of age and older. Raltegravir inhibits the catalytic activity of HIV-1 integrase, an HIV-1 encoded enzyme that is required r viral replication. Inhibition of integrase prevents the covalent insertion, or integration, of unintegrated linear HIV-1 DNA into the host cell genome preventing the formation of the HIV-1 provirus. The provirus is required to direct the production of progeny virus, so inhibiting integration prevents propagation of the viral infection. Raltegravir did not significantly inhibit human phosphoryl transferases including DNA polymerases α, β, and γ. Coadministration with others drugs that are strong inducers of UGT1A1, such as rifampin, may result in reduced plasma concentrations of raltegravir. The most common adverse reactions of moderate to severe intensity (≥2%) are insomnia, headache, dizziness, nausea and fatigue. Severe, potentially life-threatening, and fatal skin reactions have been reported. This include cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including hepatic failure. The major mechanism of clearance of raltegravir in humans is UGT1A1-mediated glucuronidation.

Originator

Curator's Comment:: Merck & Co. Inc., Istituto Di Ricerche Di Biologia Molecolar # Merck & Co. Inc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ISENTRESS

Approved Use

INDICATIONS & USAGE ISENTRESS is a human immunodeficiency virus integrase strand transfer inhibitor (HIV-1 INSTI) indicated: In combination with other antiretroviral agents for the treatment of HIV-1 infection (1). The safety and efficacy of ISENTRESS have not been established in children less than 2 years of age (1.2). ISENTRESS® is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection. This indication is based on analyses of plasma HIV-1 RNA levels in three double-blind controlled studies of ISENTRESS. Two of these studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, NRTI, PI) treatment-experienced adults through 96 weeks and one was conducted in treatment-naïve adults through 156 weeks. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response [see Clinical Studies (14)

Launch Date

1192147200000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
142 nM
400 mg 2 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RALTEGRAVIR plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1300 ng/mL
400 mg 2 times / day steady, oral
dose: 400 mg
route of administration: oral
experiment type: steady
co-administered:
RALTEGRAVIR plasma
Homo sapiens
20163 nM
1200 mg single, oral
dose: 1200 mg
route of administration: oral
experiment type: single
co-administered:
RALTEGRAVIR plasma
Homo sapiens
population: healthy
age:
sex: M
food status: Fasted
830.204 ng/ml
400 mg 2 times / day steady, oral
dose: 400 mg
route of administration: oral
experiment type: steady
co-administered:
RALTEGRAVIR unknown
Homo sapiens
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
14.3 μM × h
400 mg 2 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RALTEGRAVIR plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4070 ng*h/mL
400 mg 2 times / day steady, oral
dose: 400 mg
route of administration: oral
experiment type: steady
co-administered:
RALTEGRAVIR plasma
Homo sapiens
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9 h
400 mg 2 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RALTEGRAVIR plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
7.5 h
1200 mg single, oral
dose: 1200 mg
route of administration: oral
experiment type: single
co-administered:
RALTEGRAVIR plasma
Homo sapiens
population: healthy
age:
sex: M
food status: Fasted
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
17%
400 mg 2 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RALTEGRAVIR plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
healthy, 29 +/- 13
Health Status: healthy
Age Group: 29 +/- 13
Sex: M+F
Sources:
400 mg 2 times / day multiple, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
healthy, 29 +/- 13
Health Status: healthy
Age Group: 29 +/- 13
Sex: M+F
Sources:
24000 mg single, oral
Overdose
Dose: 24000 mg
Route: oral
Route: single
Dose: 24000 mg
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
Disc. AE: Nausea, Abdominal pain...
AEs leading to
discontinuation/dose reduction:
Nausea (mild)
Abdominal pain
Sources:
400 mg 2 times / day multiple, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy
Disc. AE: Reaction skin, Stevens-Johnson syndrome...
AEs leading to
discontinuation/dose reduction:
Reaction skin (severe|grade 4|grade 5)
Stevens-Johnson syndrome (severe|grade 4|grade 5)
Hypersensitivity reaction (severe|grade 4|grade 5)
Toxic epidermal necrolysis (severe|grade 4|grade 5)
Immune reconstitution syndrome
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain Disc. AE
24000 mg single, oral
Overdose
Dose: 24000 mg
Route: oral
Route: single
Dose: 24000 mg
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
Nausea mild
Disc. AE
24000 mg single, oral
Overdose
Dose: 24000 mg
Route: oral
Route: single
Dose: 24000 mg
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
Immune reconstitution syndrome Disc. AE
400 mg 2 times / day multiple, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy
Hypersensitivity reaction severe|grade 4|grade 5
Disc. AE
400 mg 2 times / day multiple, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy
Reaction skin severe|grade 4|grade 5
Disc. AE
400 mg 2 times / day multiple, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy
Stevens-Johnson syndrome severe|grade 4|grade 5
Disc. AE
400 mg 2 times / day multiple, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy
Toxic epidermal necrolysis severe|grade 4|grade 5
Disc. AE
400 mg 2 times / day multiple, oral
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Expanded access drug profile: raltegravir (RAL, MK-0518).
2007 Jan
[Raltegravir an integrase inhibitor--a great leap forward within reach].
2007 Nov
Mirabamides A-D, depsipeptides from the sponge Siliquariaspongia mirabilis that inhibit HIV-1 fusion.
2007 Nov
Antiviral drugs in the treatment of AIDS: what is in the pipeline ?
2007 Oct 15
Approval recommended for raltegravir in experienced patients.
2007 Sep
48-week data on raltegravir in naive patients.
2007 Sep
Raltegravir susceptibility and fitness progression of HIV type-1 integrase in patients on long-term antiretroviral therapy.
2008
Raltegravir.
2008
Raltegravir: first in class HIV integrase inhibitor.
2008 Apr
Highlights of the 15th Conference on Retroviruses and Opportunistic Infections. Advances in antiretroviral therapy.
2008 Apr-May
Preclinical evaluation of 1H-benzylindole derivatives as novel human immunodeficiency virus integrase strand transfer inhibitors.
2008 Aug
An HPLC-PDA method for the simultaneous quantification of the HIV integrase inhibitor raltegravir, the new nonnucleoside reverse transcriptase inhibitor etravirine, and 11 other antiretroviral agents in the plasma of HIV-infected patients.
2008 Dec
Integrase and integration: biochemical activities of HIV-1 integrase.
2008 Dec 17
Safe use of raltegravir and sirolimus in an HIV-infected patient with renal impairment after orthotopic liver transplantation.
2008 Feb 19
Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection.
2008 Jan
Atazanavir modestly increases plasma levels of raltegravir in healthy subjects.
2008 Jul 1
Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection.
2008 Jul 24
Raltegravir with optimized background therapy for resistant HIV-1 infection.
2008 Jul 24
Integrase inhibitors: a clinical review of raltegravir and elvitegravir.
2008 Jun
Raltegravir thorough QT/QTc study: a single supratherapeutic dose of raltegravir does not prolong the QTcF interval.
2008 Jun
Drug 9AA reactivates p21/Waf1 and Inhibits HIV-1 progeny formation.
2008 Mar 18
Complexity of interactions between voriconazole and antiretroviral agents.
2008 May
Raltegravir treatment response in an HIV-2 infected patient: a case report.
2008 May 31
Pharmacologic aspects of new antiretroviral drugs.
2008 Nov
An accurate and precise high-performance liquid chromatography method for the rapid quantification of the novel HIV integrase inhibitor raltegravir in human blood plasma after solid phase extraction.
2008 Nov 3
Raltegravir for postexposure prophylaxis following occupational exposure to HIV.
2008 Nov 30
[New CCR5 inhibitor antiretroviral drugs and integrase inhibitors].
2008 Oct
Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy.
2008 Oct
Discovery of 3-acetyl-4-hydroxy-2-pyranone derivatives and their difluoridoborate complexes as a novel class of HIV-1 integrase inhibitors.
2008 Oct 1
Selection of the Q148R integrase inhibitor resistance mutation in a failing raltegravir containing regimen.
2008 Oct 1
A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations.
2008 Sep
Clade-specific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility.
2008 Sep 12
Exacerbation of depression associated with starting raltegravir: a report of four cases.
2008 Sep 12
Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection.
2008 Sep 25
Quantitative prediction of human clearance guiding the development of Raltegravir (MK-0518, isentress) and related HIV integrase inhibitors.
2009 Apr
Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.
2009 Apr
Pharmacologic aspects of new antiretroviral drugs.
2009 Feb
Is dual therapy with raltegravir and protease inhibitors a feasible option in rescue strategy in HIV-1 infection?
2009 Feb 1
Effects of omeprazole on plasma levels of raltegravir.
2009 Feb 15
Quantification of the HIV-integrase inhibitor raltegravir and detection of its main metabolite in human plasma, dried blood spots and peripheral blood mononuclear cell lysate by means of high-performance liquid chromatography tandem mass spectrometry.
2009 Feb 20
Implications of HIV-1 M group polymorphisms on integrase inhibitor efficacy and resistance: genetic and structural in silico analyses.
2009 Jan 13
Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase.
2009 Mar
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: in Children and Adolescents: If at least 25 kg: One 400 mg film-coated tablet orally, twice daily. For patients weighing between 11 and 20 kg, either the
400 mg film-coated tablet orally, twice daily. During coadministration with rifampin in adults, 800 mg twice daily
Route of Administration: Oral
The antiviral activity of Raltegravir was determined in a cell-based HIV-1 replication assay with HeLa-CD4-LTR-β-gal cells. The highest compound concentration tested was 50 μM.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:08:20 UTC 2021
Edited
by admin
on Fri Jun 25 21:08:20 UTC 2021
Record UNII
43Y000U234
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RALTEGRAVIR POTASSIUM
JAN   MART.   ORANGE BOOK   USAN   WHO-DD  
USAN  
Official Name English
MK-0518 POTASSIUM
Code English
MK0518 POTASSIUM
Code English
POTASSIUM 4-((4-FLUOROBENZYL)CARBAMOYL)-1-METHYL-2-(1-METHYL-1-(((5-METHYL-1,3,4-OXADIAZOL-2-YL)CARBONYL)AMINO)ETHYL)-6-OXO-1,6-DIHYDROPYRIMIDIN-5-OLATE
Systematic Name English
4-PYRIMIDINECARBOXAMIDE, N-((4-FLUOROPHENYL)METHYL)-1,6-DIHYDRO-5-HYDROXY-1-METHYL-2-(1-METHYL-1-(((5-METHYL-1,3,4-OXADIAZOL-2-YL)CARBONYL)AMINO)ETHYL)-6-OXO-, MONOPOTASSIUM SALT
Common Name English
RALTEGRAVIR POTASSIUM [JAN]
Common Name English
RALTEGRAVIR POTASSIUM [ORANGE BOOK]
Common Name English
RALTEGRAVIR POTASSIUM [USP MONOGRAPH]
Common Name English
RALTEGRAVIR POTASSIUM [USAN]
Common Name English
RALTEGRAVIR POTASSIUM [USP-RS]
Common Name English
RALTEGRAVIR POTASSIUM COMPONENT OF DUTREBIS
Brand Name English
RALTEGRAVIR POTASSIUM [MART.]
Common Name English
RALTEGRAVIR POTASSIUM SALT
Common Name English
RALTEGRAVIR POTASSIUM [EP MONOGRAPH]
Common Name English
RALTEGRAVIR POTASSIUM [WHO-DD]
Common Name English
RALTEGRAVIR MONOPOTASSIUM SALT
MI  
Common Name English
DUTREBIS COMPONENT RALTEGRAVIR POTASSIUM
Brand Name English
RALTEGRAVIR MONOPOTASSIUM SALT [MI]
Common Name English
ISENTRESS
Brand Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS DUTREBIX (AUTHORIZED: HIV INFECTIONS)
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
EMA ASSESSMENT REPORTS ISENTRESS (AUTHORIZED: HIV INFECTIONS)
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
Code System Code Type Description
CAS
871038-72-1
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY
DRUG BANK
DBSALT000924
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY
PUBCHEM
23668479
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY
MERCK INDEX
M9486
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL254316
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY
JAPANESE REVIEW
ISENTRESS
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY APPROVED JUNE 2008
EVMPD
SUB25668
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY
USP_CATALOG
1598278
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY USP-RS
FDA UNII
43Y000U234
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY
RXCUI
1235585
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C73823
Created by admin on Fri Jun 25 21:08:20 UTC 2021 , Edited by admin on Fri Jun 25 21:08:20 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
correction factor: multiply the peak area of impurity C by 1.6
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY