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Details

Stereochemistry ACHIRAL
Molecular Formula C20H21FN6O5
Molecular Weight 444.4163
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Raltegravir

SMILES

CN1C(=O)C(O)=C(N=C1C(C)(C)NC(=O)C2=NN=C(C)O2)C(=O)NCC3=CC=C(F)C=C3

InChI

InChIKey=CZFFBEXEKNGXKS-UHFFFAOYSA-N
InChI=1S/C20H21FN6O5/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)

HIDE SMILES / InChI

Molecular Formula C20H21FN6O5
Molecular Weight 444.4163
Charge 0
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
10.0 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

2007
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
830.204 ng/ml
400 mg 2 times / day multiple, oral
dose: 400 mg
route of administration: oral
experiment type: MULTIPLE
co-administered:
RALTEGRAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
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
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
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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
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
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
Raltegravir (MK-0518): an integrase inhibitor for the treatment of HIV-1.
2007 Dec
Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase.
2007 Nov 12
Antiviral drugs in the treatment of AIDS: what is in the pipeline ?
2007 Oct 15
How will CCR5 antagonists influence the recommendations for the antiretroviral treatment of HIV-1 infection.
2007 Oct 15
48-week data on raltegravir in naive patients.
2007 Sep
Raltegravir, an HIV-1 integrase inhibitor for HIV infection.
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
Novel druggable hot spots in avian influenza neuraminidase H5N1 revealed by computational solvent mapping of a reduced and representative receptor ensemble.
2008 Feb
Lack of a pharmacokinetic effect of raltegravir on midazolam: in vitro/in vivo correlation.
2008 Feb
Tricyclic HIV integrase inhibitors: potent and orally bioavailable C5-aza analogs.
2008 Feb 15
Ensemble-based virtual screening reveals potential novel antiviral compounds for avian influenza neuraminidase.
2008 Jul 10
An improved relaxed complex scheme for receptor flexibility in computer-aided drug design.
2008 Sep
Comparing two integrase inhibitors. The first head-to-head study comparing raltegravir and elvitegravir.
2008 Sep-Oct
Is dual therapy with raltegravir and protease inhibitors a feasible option in rescue strategy in HIV-1 infection?
2009 Feb 1
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 chewable tablet or the formulation for oral suspension can be used.
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 Mon Mar 31 18:17:09 GMT 2025
Edited
by admin
on Mon Mar 31 18:17:09 GMT 2025
Record UNII
22VKV8053U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Raltegravir
DASH   EMA EPAR   INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
L-000900612
Preferred Name English
RALTEGRAVIR [MART.]
Common Name English
L000900612
Code English
RALTEGRAVIR [VANDF]
Common Name English
Raltegravir [WHO-DD]
Common Name English
MK-0518
Code English
RALTEGRAVIR [MI]
Common Name English
RALTEGRAVIR [EMA EPAR]
Common Name English
N-(4-FLUOROBENZYL)-5-HYDROXY-1-METHYL-2-(1-METHYL-1-(((5-METHYL-1,3,4-OXADIAZOL-2-YL)CARBONYL)AMINO)ETHYL)-6-OXO-1,6-DIHYDROPYRIMIDINE-4-CARBOXAMIDE
Systematic Name English
raltegravir [INN]
Common 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-
Systematic Name English
N-(2-(4-(4-FLUOROBENZYLCARBAMOYL)-5-HYDROXY-1-METHYL-6-OXO-1,6- DIHYDROPYRIMIDIN-2-YL)PROPAN-2-YL)-5-METHYL-1,3,4-OXADIAZOLE-2-CARBOXAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C281
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
WHO-ATC J05AX08
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
NDF-RT N0000175887
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
WHO-ATC J05AR16
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
EMA ASSESSMENT REPORTS ISENTRESS (AUHTORIZED: HIV INFECTIONS)
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
LIVERTOX NBK548313
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
WHO-VATC QJ05AX08
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
NDF-RT N0000000127
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
Code System Code Type Description
EVMPD
SUB25667
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
INN
8842
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
CAS
518048-05-0
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
PUBCHEM
54671008
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
NCI_THESAURUS
C72837
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
CHEBI
82960
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
DAILYMED
22VKV8053U
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
MESH
C507898
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
DRUG CENTRAL
2352
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
HSDB
8124
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
LACTMED
Raltegravir
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
MERCK INDEX
m9486
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY Merck Index
USAN
TT-71
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
EPA CompTox
DTXSID2048660
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
DRUG BANK
DB06817
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
SMS_ID
100000091686
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
ChEMBL
CHEMBL254316
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
WIKIPEDIA
RALTEGRAVIR
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
FDA UNII
22VKV8053U
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY
RXCUI
719872
Created by admin on Mon Mar 31 18:17:09 GMT 2025 , Edited by admin on Mon Mar 31 18:17:09 GMT 2025
PRIMARY RxNorm
Related Record Type Details
EXCRETED UNCHANGED
Following administration of a single dose of 200 mg [14 C] raltegravir to young healthy subjects (Protocol 011), approximately 83.0% of the radioactivity dose was recovered, with 51.1% in feces and 31.8% in-urine over a 10-day period.
AMOUNT EXCRETED
URINE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET ORGANISM->INHIBITOR
TRANSPORTER -> SUBSTRATE
LABELED -> NON-LABELED
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
MINOR
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE INACTIVE -> PARENT
MAJOR
FECAL; URINE
Related Record Type Details
IMPURITY -> PARENT
This is a process impurity controlled in the drug substance and not monitored in the drug product [USP]
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

SINGLE DOSE

FASTED CONDITION

Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC