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
Structure for Raltegravir (DB06817)
- 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.
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- Associated Therapies
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism AIntegrase inhibitorHuman 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 outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcipimox The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Raltegravir is combined with Acipimox. Adenine The metabolism of Raltegravir 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 Raltegravir. Alendronic acid The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Alendronic acid is combined with Raltegravir. Almasilate The serum concentration of Raltegravir can be decreased when it is combined with Almasilate. Aluminium Aluminium can cause an increase in the absorption of Raltegravir resulting in an increased serum concentration and potentially a worsening of adverse effects. Aluminium phosphate Aluminium phosphate can cause a decrease in the absorption of Raltegravir resulting in a reduced serum concentration and potentially a decrease in efficacy. Aluminum chloride Aluminum chloride can cause a decrease in the absorption of Raltegravir resulting in a reduced serum concentration and potentially a decrease in efficacy. Aluminum hydroxide Aluminum hydroxide can cause a decrease in the absorption of Raltegravir resulting in a reduced serum concentration and potentially a decrease in efficacy. Aluminum sulfate Aluminum sulfate can cause a decrease in the absorption of Raltegravir resulting in a reduced serum concentration and potentially a decrease in efficacy. 
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- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Raltegravir potassium 43Y000U234 871038-72-1 IFUKBHBISRAZTF-UHFFFAOYSA-M - Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Isentress Tablet, film coated 400 mg/1 Oral H.J. Harkins Company 2017-07-31 Not applicable US 
Isentress Tablet, chewable 100 mg Oral Merck Ltd. 2013-02-11 Not applicable Canada 
Isentress Tablet, film coated 400 mg/1 Oral REMEDYREPACK INC. 2016-08-29 2018-09-17 US Isentress Tablet, film coated 400 mg/1 Oral Dispensing Solutions, Inc. 2007-10-12 Not applicable US 
Isentress Tablet, film coated 400 mg/1 Oral REMEDYREPACK INC. 2018-10-31 Not applicable US Isentress Tablet, film coated 600 mg Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU 
Isentress Granule, for suspension 100 mg/1 Oral Merck Sharp & Dohme Corp. 2013-12-20 Not applicable US Isentress Tablet, chewable 100 mg Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU Isentress Tablet, film coated 400 mg/1 Oral Merck Sharp & Dohme Corp. 2007-10-12 Not applicable US 
Isentress Tablet, film coated 400 mg Oral Merck Sharp & Dohme B.V. 2020-12-16 Not applicable EU
Categories
- ATC Codes
- J05AR16 — Lamivudine and raltegravir
- J05AR — Antivirals for treatment of HIV infections, combinations
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- Drug Categories
- Agents Causing Muscle Toxicity
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals used in combination for the treatment of HIV infections
- Direct Acting Antivirals
- Enzyme Inhibitors
- HIV Integrase Inhibitors
- Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor
- Integrase Inhibitors
- Pyrrolidines
- Pyrrolidinones
- UGT1A1 Substrates
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- O'Neal R: MK-0518 and GS-9137: two promising integrase inhibitors in the pipeline. BETA. 2006 Summer;18(4):13-6. [Article]
- James JS: Integrase inhibitor MK-0518: Merck opens expanded-access program. AIDS Treat News. 2006 Jul-Sep;(419):5. [Article]
- 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]
- Colquitt AR, Pham PA: Expanded access drug profile: raltegravir (RAL, MK-0518). Hopkins HIV Rep. 2007 Jan;19(1):11-2. [Article]
- Authors unspecified: Raltegravir demonstrates potency. AIDS Patient Care STDS. 2007 Apr;21(4):288. [Article]
- Authors unspecified: Anti-HIV agents. Raltegravir--other issues. TreatmentUpdate. 2007 Feb;19(2):9-10. [Article]
- Authors unspecified: Anti-HIV agents. Integrase inhibitor raltegravir makes its mark. TreatmentUpdate. 2007 Feb;19(2):8-9. [Article]
- Cahn P, Sued O: Raltegravir: a new antiretroviral class for salvage therapy. Lancet. 2007 Apr 14;369(9569):1235-6. [Article]
- External Links
- KEGG Drug
- D06676
- PubChem Compound
- 54671008
- PubChem Substance
- 175427095
- ChemSpider
- 16445111
- BindingDB
- 25351
- 719872
- ChEMBL
- CHEMBL254316
- ZINC
- ZINC000013831130
- PDBe Ligand
- RLT
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Raltegravir
- PDB Entries
- 3l2v / 3oya / 4mda / 4mdb / 7lw6 / 7oug
- FDA label
- Download (127 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Not Available Healthy Subjects (HS) 1 4 Completed Basic Science Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Health Services Research Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Prevention Human Immunodeficiency Virus (HIV) Infections 6 4 Completed Treatment Adverse Drug Reaction (ADR) / Human Immunodeficiency Virus (HIV) Infections / Quality of Life (QOL) 1 4 Completed Treatment Aging-related Inflammation in HIV-infected Patients 1 4 Completed Treatment Cardiovascular Disease (CVD) / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Treatment Cardiovascular Disease (CVD) / Human Immunodeficiency Virus (HIV) Infections / Inflammation 1 4 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Treatment Fatty Liver / HIV Seropositivity / Syndrome, Metabolic 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral Granule, for suspension Oral 100 mg/1 Granule, for suspension Oral 100 MG Tablet Oral 100 MG Tablet Oral 25 MG Tablet Oral 400 mg Tablet, chewable Oral 100 mg/1 Tablet, chewable Oral 25 mg/1 Tablet, film coated Oral 400 MG Tablet, film coated Oral 400 mg/1 Tablet, film coated Oral 600 MG Tablet, film coated Oral 600 mg/1 Tablet, film coated Oral Tablet Oral 600 mg Granule Oral 100 mg Tablet, chewable Oral 100 mg Tablet, chewable Oral 25 mg Powder Not applicable 1 kg/1kg Tablet, coated Oral 400 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7217713 Yes 2007-05-15 2023-04-21 US US7435734 Yes 2008-10-14 2023-04-21 US US7754731 Yes 2010-07-13 2029-09-11 US US7169780 Yes 2007-01-30 2024-04-03 US US7820660 No 2010-10-26 2023-04-25 US US9649311 Yes 2017-05-16 2031-04-21 US US10772888 No 2012-03-30 2032-03-30 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source logP -0.39 ChemAxon pKa (Strongest Acidic) 5.62 ChemAxon pKa (Strongest Basic) -1.5 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 150.02 Å2 ChemAxon Rotatable Bond Count 6 ChemAxon Refractivity 112.59 m3·mol-1 ChemAxon Polarizability 42.47 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes 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 Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-01ot-0417900000-7f0f52f17ac409473482 MS/MS Spectrum - , positive LC-MS/MS splash10-014i-0011900000-1f750fd89ed368c2519a
Targets
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- 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
- 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]
- 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
- 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]
- 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]
- 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 on September 14, 2010 16:21 / Updated on September 16, 2021 13:04