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
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)
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.
CNS Activity
Originator
Sources: https://www.google.com/patents/WO2006060712A2?cl=en
Curator's Comment: Merck & Co. Inc., Istituto Di Ricerche Di Biologia Molecolar # Merck & Co. Inc.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3471 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=24793360 |
10.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ISENTRESS Approved UseINDICATIONS & 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 Date2007 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1300 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01785160 |
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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03537404 |
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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03667547 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4070 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01785160 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.5 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03667547 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
800 mg single, oral Highest studied dose |
healthy, 29 +/- 13 |
|
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 |
|
24000 mg single, oral Overdose Dose: 24000 mg Route: oral Route: single Dose: 24000 mg Sources: |
unhealthy, 42 |
Disc. AE: Nausea, Abdominal pain... AEs leading to discontinuation/dose reduction: Nausea (mild) Sources: Abdominal pain |
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 Health Status: unhealthy Sources: |
Disc. AE: Reaction skin, Stevens-Johnson syndrome... AEs leading to discontinuation/dose reduction: Reaction skin (severe|grade 4|grade 5) Sources: 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 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Abdominal pain | Disc. AE | 24000 mg single, oral Overdose Dose: 24000 mg Route: oral Route: single Dose: 24000 mg Sources: |
unhealthy, 42 |
Nausea | mild Disc. AE |
24000 mg single, oral Overdose Dose: 24000 mg Route: oral Route: single Dose: 24000 mg Sources: |
unhealthy, 42 |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
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 Health Status: unhealthy Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022145s035,203045s012,205786s003lbl.pdf
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25629256
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
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on
Edited
Mon Mar 31 18:17:09 GMT 2025
by
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Mon Mar 31 18:17:09 GMT 2025
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Record UNII |
22VKV8053U
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C281
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WHO-ATC |
J05AX08
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NDF-RT |
N0000175887
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WHO-ATC |
J05AR16
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EMA ASSESSMENT REPORTS |
ISENTRESS (AUHTORIZED: HIV INFECTIONS)
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LIVERTOX |
NBK548313
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WHO-VATC |
QJ05AX08
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NDF-RT |
N0000000127
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SUB25667
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C72837
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8124
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Raltegravir
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m9486
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TT-71
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CHEMBL254316
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RALTEGRAVIR
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22VKV8053U
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719872
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PRIMARY | RxNorm |
Related Record | Type | Details | ||
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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
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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TARGET ORGANISM->INHIBITOR |
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TRANSPORTER -> SUBSTRATE | |||
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LABELED -> NON-LABELED |
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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SALT/SOLVATE -> PARENT |
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Related Record | Type | Details | ||
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METABOLITE INACTIVE -> PARENT |
MAJOR
FECAL; URINE
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
This is a process impurity controlled in the drug substance and not monitored in the drug product [USP]
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IMPURITY -> PARENT |
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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Biological Half-life | PHARMACOKINETIC |
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Elimination PHARMACOKINETIC |
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