Raltegravir

Identification

Summary

Raltegravir is an antiretroviral agent used for the treatment of HIV infections in conjunction with other antiretrovirals.

Brand Names
Isentress
Generic Name
Raltegravir
DrugBank Accession Number
DB06817
Background

Raltegravir is an antiretroviral drug produced by Merck & Co., used to treat HIV infection. It received approval by the U.S. Food and Drug Administration (FDA) on 12 October 2007, the first of a new class of HIV drugs, the integrase inhibitors, to receive such approval.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 444.4163
Monoisotopic: 444.155746017
Chemical Formula
C20H21FN6O5
Synonyms
  • Raltegravir

Pharmacology

Indication

For the treatment of HIV-1 infection in conjunction with other antiretrovirals.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatHuman immunodeficiency virus type 1 (hiv-1) infection••••••••••••••••••••••••• •••••• •• ••••••••••••• ••••••• ••••••••• ••••••• •••• ••••••
Used in combination to treatHuman immunodeficiency virus type 1 (hiv-1) infection•••••••••••••••••••••••••••• ••••••• ••••••••• ••••••• •••• ••••••
Associated Therapies
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Not Available

Mechanism of action

Raltegravir inhibits HIV integrase to prevent the viral genome being incorporated into the human genome. Raltegravir is primarily metabolized by glucuronidation.

TargetActionsOrganism
AIntegrase
inhibitor
Human immunodeficiency virus 1
Absorption

Absorbed from the gastrointestinal tract.

Volume of distribution

Approximately 83% bound to human plasma protein and is minimally distributed into red blood cells (blood-to-plasma partitioning ratio of 0.6).

Protein binding

83%

Metabolism

Hepatic (UGT1A1)

Route of elimination

Feces and urine

Half-life

9 hours

Clearance

The major mechanism of clearance of raltegravir in humans is glucuronidation mediated by UGT1A1, the renal clearance of unchanged drug is a minor pathway of elimination of raltegravir (9% of total dose).

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Raltegravir is combined with Acipimox.
AdenineThe metabolism of Raltegravir can be decreased when combined with Adenine.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Raltegravir.
Alendronic acidThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Alendronic acid is combined with Raltegravir.
AlmasilateThe serum concentration of Raltegravir can be decreased when it is combined with Almasilate.
Food Interactions
  • Take with or without food.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Raltegravir potassium43Y000U234871038-72-1IFUKBHBISRAZTF-UHFFFAOYSA-M
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IsentressTablet, film coated400 mgOralMerck Sharp & Dohme B.V.2020-12-16Not applicableEU flag
IsentressTablet, film coated400 mg/1OralH.J. Harkins Company2017-07-31Not applicableUS flag
IsentressTablet, film coated400 mg/1OralPharmasource Meds, LLC2023-03-03Not applicableUS flag
IsentressTablet, film coated400 mg/1OralDispensing Solutions, Inc.2007-10-12Not applicableUS flag
IsentressTablet, chewable25 mgOralMerck Ltd.2013-02-11Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
DUTREBISRaltegravir (300 MG) + Lamivudine (150 MG)Tablet, film coatedOralOrganon Pharma (Uk) Limited2015-06-272022-08-19Italy flag

Categories

ATC Codes
J05AR16 — Lamivudine and raltegravirJ05AJ01 — Raltegravir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrimidinecarboxylic acids and derivatives. These are compounds containing a pyrimidine ring which bears a carboxylic acid group (or a derivative thereof).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Pyrimidinecarboxylic acids and derivatives
Alternative Parents
2-heteroaryl carboxamides / Pyrimidones / Fluorobenzenes / Hydroxypyrimidines / Aryl fluorides / Hydropyrimidines / Vinylogous acids / 1,3,4-oxadiazoles / Heteroaromatic compounds / Secondary carboxylic acid amides
show 9 more
Substituents
1,3,4-oxadiazole / 2-heteroaryl carboxamide / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzenoid / Carboxamide group / Carboxylic acid derivative
show 22 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, pyrimidines, 1,2,4-oxadiazole, dicarboxylic acid amide (CHEBI:82960)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
22VKV8053U
CAS number
518048-05-0
InChI Key
CZFFBEXEKNGXKS-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-{2-[(5-methyl-1,3,4-oxadiazol-2-yl)formamido]propan-2-yl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide
SMILES
CN1C(=O)C(O)=C(N=C1C(C)(C)NC(=O)C1=NN=C(C)O1)C(=O)NCC1=CC=C(F)C=C1

References

General References
  1. Nachman S, Zheng N, Acosta EP, Teppler H, Homony B, Graham B, Fenton T, Xu X, Wenning L, Spector SA, Frenkel LM, Alvero C, Worrell C, Handelsman E, Wiznia A: Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years. Clin Infect Dis. 2014 Feb;58(3):413-22. doi: 10.1093/cid/cit696. Epub 2013 Oct 21. [Article]
  2. Barau C, Furlan V, Yazdanpanah Y, Fagard C, Molina JM, Taburet AM, Barrail-Tran A: Characterization of binding of raltegravir to plasma proteins. Antimicrob Agents Chemother. 2013 Oct;57(10):5147-50. doi: 10.1128/AAC.00625-13. Epub 2013 Jul 15. [Article]
  3. Arora R, de Beauchene IC, Polanski J, Laine E, Tchertanov L: Raltegravir flexibility and its impact on recognition by the HIV-1 IN targets. J Mol Recognit. 2013 Sep;26(9):383-401. doi: 10.1002/jmr.2277. [Article]
  4. Eron JJ, Cooper DA, Steigbigel RT, Clotet B, Gatell JM, Kumar PN, Rockstroh JK, Schechter M, Markowitz M, Yeni P, Loutfy MR, Lazzarin A, Lennox JL, Strohmaier KM, Wan H, Barnard RJ, Nguyen BY, Teppler H: Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: final results of two randomised, placebo-controlled trials. Lancet Infect Dis. 2013 Jul;13(7):587-96. doi: 10.1016/S1473-3099(13)70093-8. Epub 2013 May 7. [Article]
  5. Winston A, Mallon PW, Boffito M: The clinical pharmacology of antiretrovirals in development. Expert Opin Drug Metab Toxicol. 2006 Jun;2(3):447-58. [Article]
  6. O'Neal R: MK-0518 and GS-9137: two promising integrase inhibitors in the pipeline. BETA. 2006 Summer;18(4):13-6. [Article]
  7. James JS: Integrase inhibitor MK-0518: Merck opens expanded-access program. AIDS Treat News. 2006 Jul-Sep;(419):5. [Article]
  8. Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H: Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. [Article]
  9. Colquitt AR, Pham PA: Expanded access drug profile: raltegravir (RAL, MK-0518). Hopkins HIV Rep. 2007 Jan;19(1):11-2. [Article]
  10. Authors unspecified: Raltegravir demonstrates potency. AIDS Patient Care STDS. 2007 Apr;21(4):288. [Article]
  11. Authors unspecified: Anti-HIV agents. Raltegravir--other issues. TreatmentUpdate. 2007 Feb;19(2):9-10. [Article]
  12. Authors unspecified: Anti-HIV agents. Integrase inhibitor raltegravir makes its mark. TreatmentUpdate. 2007 Feb;19(2):8-9. [Article]
  13. Cahn P, Sued O: Raltegravir: a new antiretroviral class for salvage therapy. Lancet. 2007 Apr 14;369(9569):1235-6. [Article]
  14. FDA Approved Drug Products: ISENTRESS (raltegravir) oral suspension and tablets [Link]
KEGG Drug
D06676
PubChem Compound
54671008
PubChem Substance
175427095
ChemSpider
16445111
BindingDB
25351
RxNav
719872
ChEBI
82960
ChEMBL
CHEMBL254316
ZINC
ZINC000013831130
PDBe Ligand
RLT
Drugs.com
Drugs.com Drug Page
Wikipedia
Raltegravir
PDB Entries
3l2v / 4mda / 4mdb / 7lw6 / 7m0n / 7oug
FDA label
Download (127 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral
Granule, for suspensionOral100 MG
Granule, for suspensionOral100 mg/1
TabletOral100 MG
TabletOral25 MG
TabletOral400 mg
Tablet, chewableOral100 mg
Tablet, chewableOral100 mg/1
Tablet, chewableOral25 mg/1
Tablet, chewableOral25 mg
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral600 mg/1
Tablet, film coatedOral
Tablet, film coatedOral600 mg
Tablet, film coatedOral400 mg
TabletOral600 mg
GranuleOral100 mg
PowderNot applicable1 kg/1kg
Tablet, coatedOral400 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7217713Yes2007-05-152023-04-21US flag
US7435734Yes2008-10-142023-04-21US flag
US7754731Yes2010-07-132029-09-11US flag
US7169780Yes2007-01-302024-04-03US flag
US7820660No2010-10-262023-04-25US flag
US9649311Yes2017-05-162031-04-21US flag
US10772888No2020-09-152032-03-30US flag
US8771733No2014-07-082030-06-02US flag
US8852632No2014-10-072028-01-28US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0976 mg/mLALOGPS
logP1.3ALOGPS
logP-0.39Chemaxon
logS-3.7ALOGPS
pKa (Strongest Acidic)7.02Chemaxon
pKa (Strongest Basic)-1.1Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area150.02 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity112.59 m3·mol-1Chemaxon
Polarizability42.45 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-014i-0011900000-1f750fd89ed368c2519a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01ot-0417900000-7f0f52f17ac409473482
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0011900000-1f750fd89ed368c2519a
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00dj-0009500000-26a8f54d48aea57707b8
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-006x-6319500000-fe3f71303a26392c077b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00dl-0229300000-95c9dc1735afbf3cf0b6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0g4i-6669300000-d4ebb4258b1464c03b23
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0kmj-1689200000-15f416664f9ac6251029
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00l6-9411100000-9cbafc2e930d4a578762
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-202.82045
predicted
DeepCCS 1.0 (2019)
[M+H]+205.21602
predicted
DeepCCS 1.0 (2019)
[M+Na]+211.16913
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q7ZJM1
Uniprot Name
Integrase
Molecular Weight
32226.645 Da
References
  1. Evering TH, Markowitz M: Raltegravir: an integrase inhibitor for HIV-1. Expert Opin Investig Drugs. 2008 Mar;17(3):413-22. doi: 10.1517/13543784.17.3.413 . [Article]
  2. Anker M, Corales RB: Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection. Expert Opin Investig Drugs. 2008 Jan;17(1):97-103. [Article]

Enzymes

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
References
  1. Wenning LA, Petry AS, Kost JT, Jin B, Breidinger SA, DeLepeleire I, Carlini EJ, Young S, Rushmore T, Wagner F, Lunde NM, Bieberdorf F, Greenberg H, Stone JA, Wagner JA, Iwamoto M: Pharmacokinetics of raltegravir in individuals with UGT1A1 polymorphisms. Clin Pharmacol Ther. 2009 Jun;85(6):623-7. doi: 10.1038/clpt.2009.12. Epub 2009 Mar 11. [Article]
  2. Wenning LA, Hanley WD, Brainard DM, Petry AS, Ghosh K, Jin B, Mangin E, Marbury TC, Berg JK, Chodakewitz JA, Stone JA, Gottesdiener KM, Wagner JA, Iwamoto M: Effect of rifampin, a potent inducer of drug-metabolizing enzymes, on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother. 2009 Jul;53(7):2852-6. doi: 10.1128/AAC.01468-08. Epub 2009 May 11. [Article]
  3. Anker M, Corales RB: Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection. Expert Opin Investig Drugs. 2008 Jan;17(1):97-103. [Article]

Drug created at September 14, 2010 16:21 / Updated at March 28, 2024 03:23