Raltegravir

Identification

Name

Raltegravir

Accession Number

DB06817

Description

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

Similar Structures

Weight: Average: 444.4163
Monoisotopic: 444.155746017
Chemical Formula: C₂₀H₂₁FN₆O₅

Synonyms

Raltegravir

Pharmacology

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Drug Discovery

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Indication

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

Associated Conditions

Human Immunodeficiency Virus Type 1 (HIV-1) Infection

Associated Therapies

Post-exposure prophylaxis for occupational exposure to HIV therapy

Contraindications & Blackbox Warnings

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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	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

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Toxicity

Not Available

Affected organisms

Human Immunodeficiency Virus

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
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Acipimox	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	The serum concentration of Raltegravir can be decreased when it is combined with Aluminium phosphate.
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	The serum concentration of Raltegravir can be decreased when it is combined with Aluminum hydroxide.
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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Food Interactions

Take with or without food.

Products

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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
Isentress	Tablet, film coated	400 mg/1	Oral	Direct_Rx	2019-08-13	Not applicable
Isentress	Tablet	400 mg	Oral	Merck Ltd.	2007-11-28	Not applicable
Isentress	Tablet, film coated	600 mg/1	Oral	Merck Sharp & Dohme Corp.	2017-05-26	Not applicable
Isentress	Tablet, film coated	400 mg/1	Oral	Nucare Pharmaceuticals,inc.	2007-10-12	Not applicable
Isentress	Granule	100 mg	Oral	Merck Sharp & Dohme B.V.	2020-12-16	Not applicable
Isentress	Tablet, film coated	400 mg/1	Oral	A-S Medication Solutions	2007-10-12	Not applicable
Isentress	Tablet, film coated	400 mg	Oral	Merck Sharp & Dohme B.V.	2020-12-16	Not applicable
Isentress	Tablet, chewable	100 mg/1	Oral	Merck Sharp & Dohme Corp.	2011-12-21	Not applicable
Isentress	Tablet, film coated	400 mg/1	Oral	State of Florida DOH Central Pharmacy	2009-07-01	Not applicable
Isentress	Tablet, chewable	100 mg	Oral	Merck Ltd.	2013-02-11	Not applicable

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. [PubMed:24145879]
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. [PubMed:23856784]
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. [PubMed:23836466]
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. [PubMed:23664333]
Winston A, Mallon PW, Boffito M: The clinical pharmacology of antiretrovirals in development. Expert Opin Drug Metab Toxicol. 2006 Jun;2(3):447-58. [PubMed:16863445]
O'Neal R: MK-0518 and GS-9137: two promising integrase inhibitors in the pipeline. BETA. 2006 Summer;18(4):13-6. [PubMed:17019786]
James JS: Integrase inhibitor MK-0518: Merck opens expanded-access program. AIDS Treat News. 2006 Jul-Sep;(419):5. [PubMed:17096488]
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. [PubMed:17133211]
Colquitt AR, Pham PA: Expanded access drug profile: raltegravir (RAL, MK-0518). Hopkins HIV Rep. 2007 Jan;19(1):11-2. [PubMed:17569171]
Authors unspecified: Raltegravir demonstrates potency. AIDS Patient Care STDS. 2007 Apr;21(4):288. [PubMed:17506141]
Authors unspecified: Anti-HIV agents. Raltegravir--other issues. TreatmentUpdate. 2007 Feb;19(2):9-10. [PubMed:17447317]
Authors unspecified: Anti-HIV agents. Integrase inhibitor raltegravir makes its mark. TreatmentUpdate. 2007 Feb;19(2):8-9. [PubMed:17447316]
Cahn P, Sued O: Raltegravir: a new antiretroviral class for salvage therapy. Lancet. 2007 Apr 14;369(9569):1235-6. [PubMed:17434380]

External Links

KEGG Drug: D06676
PubChem Compound: 54671008
PubChem Substance: 175427095
ChemSpider: 16445111
BindingDB: 25351
RxNav: 719872
ChEMBL: CHEMBL254316
ZINC: ZINC000013831130
PDBe Ligand: RLT
Drugs.com: Drugs.com Drug Page
Wikipedia: Raltegravir

AHFS Codes

08:18.08.12 — HIV Integrase Inhibitors

PDB Entries

3l2v / 3oya / 4mda / 4mdb

FDA label

Download (127 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Not Available	Healthy Volunteers	1
4	Completed	Basic Science	Hepatitis C Viral 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	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 / Inflammatory Reaction	1
4	Completed	Treatment	Fatty Liver / HIV Seropositivity / Metabolic Syndromes	1
4	Completed	Treatment	HCV Coinfection / Human Immunodeficiency Virus (HIV) Infections	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet, film coated	Oral
Tablet, film coated	Oral	150 MG
Granule, for suspension	Oral	100 MG
Granule, for suspension	Oral	100 mg/1
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/1
Tablet, film coated	Oral	600 mg/1
Tablet, film coated	Oral	600 mg
Tablet, coated	Oral	400 mg
Tablet, film coated	Oral	400 mg
Tablet	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

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US7217713	Yes	2007-05-15	2023-04-21
US7435734	Yes	2008-10-14	2023-04-21
US7754731	Yes	2010-07-13	2029-09-11
US7169780	Yes	2007-01-30	2024-04-03
US7820660	No	2010-10-26	2023-04-25
US9649311	Yes	2017-05-16	2031-04-21
US10772888	No	2012-03-30	2032-03-30

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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Details1. Integrase

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 . [PubMed:18321239]
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. [PubMed:18095922]

Enzymes

Details1. UDP-glucuronosyltransferase 1-1

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. [PubMed:19279563]
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. [PubMed:19433563]
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. [PubMed:18095922]

Drug created on September 14, 2010 16:21 / Updated on March 01, 2021 12:05

Raltegravir

Identification

Structure for Raltegravir (DB06817)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets

References

Enzymes

References