Linezolid
Identification
- Name
- Linezolid
- Accession Number
- DB00601
- Description
Linezolid is a synthetic antibiotic, the first of the oxazolidinone class, used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA). The drug works by inhibiting the initiation of bacterial protein synthesis.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Linezolid (DB00601)
- Weight
- Average: 337.3461
Monoisotopic: 337.143784348 - Chemical Formula
- C16H20FN3O4
- Synonyms
- Linezolid
- Linezolide
- Linezolidum
- N-(((S)-3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl)methyl)acetamide
- External IDs
- INF 0026
- PNU 100766
- U 100
- U 100766
- U 766
- U-100,766
- U-100766
Pharmacology
- Indication
For the treatment of bacterial infections caused by susceptible strains of vancomycin resistant Enterococcus faecium, Staphylococcal aureus (methicillin resistant and susceptible strains), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae.
- Associated Conditions
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
Linezolid is a synthetic antibacterial agent of a new class of antibiotics, the oxazolidinones, which has clinical utility in the treatment of infections caused by aerobic Gram-positive bacteria. The in vitro spectrum of activity of linezolid also includes certain Gram-negative bacteria and anaerobic bacteria. Susceptible organisms include methicillin- and vancomycin-resistant staphylococci, vancomycin-resistant enterococci, penicillin-resistant pneumococci and anaerobes. Oxazolidinones inhibit protein synthesis by binding at the P site at the ribosomal 50S subunit. Resistance to other protein synthesis inhibitors does not affect oxazolidinone activity, however rare development of oxazolidinone resistance cases, associated with 23S rRNA alterations during treatment have been reported. Linezolid inhibits bacterial protein synthesis through a mechanism of action different from that of other antibacterial agents; therefore, cross-resistance between linezolid and other classes of antibiotics is unlikely.
- Mechanism of action
Linezolid is a synthetic antibacterial agent of the oxazolidinone class of antibiotics. It has in vitro activity against aerobic Gram positive bacteria, certain Gram negative bacteria and anaerobic microorganisms. It selectively inhibits bacterial protein synthesis through binding to sites on the bacterial ribosome and prevents the formation of a functional 70S-initiation complex. Specifically, linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. The results of time-kill studies have shown linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, linezolid was found to be bactericidal for the majority of strains. Linezolid is also a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.
Target Actions Organism A23S ribosomal RNA inhibitorEnteric bacteria and other eubacteria - Absorption
Linezolid is rapidly and extensively absorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing, and the absolute bioavailability is approximately 100%.
- Volume of distribution
- 40 to 50 L [healthy adult volunteers]
- Protein binding
31%
- Metabolism
Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: the aminoethoxyacetic acid metabolite (A), and the hydroxyethyl glycine metabolite
Hover over products below to view reaction partners
- Route of elimination
- Not Available
- Half-life
4.5-5.5 hours
- Clearance
- Not Available
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
Clinical signs of acute toxicity lead to decreased activity, ataxia, vomiting and tremors.
- Affected organisms
- Gram negative and gram positive bacteria
- 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 Unlock Additional DataAbatacept The risk or severity of adverse effects can be increased when Linezolid is combined with Abatacept. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Linezolid is combined with Abciximab. Acarbose Linezolid may increase the hypoglycemic activities of Acarbose. Acebutolol The risk or severity of hypertension can be increased when Linezolid is combined with Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Linezolid is combined with Aceclofenac. Acemetacin The risk or severity of hypertension can be increased when Linezolid is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding and hemorrhage can be increased when Linezolid is combined with Acenocoumarol. Acetazolamide The risk or severity of adverse effects can be increased when Linezolid is combined with Acetazolamide. Acetohexamide Linezolid may increase the hypoglycemic activities of Acetohexamide. Acetophenazine The risk or severity of extrapyramidal symptoms can be increased when Linezolid is combined with Acetophenazine. Additional Data Available- Extended DescriptionExtended DescriptionAvailable for Purchase
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - SeveritySeverityAvailable for Purchase
A severity rating for each drug interaction, from minor to major.
Learn more - Evidence LevelEvidence LevelAvailable for Purchase
A rating for the strength of the evidence supporting each drug interaction.
Learn more - ActionActionAvailable for Purchase
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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- Food Interactions
- Avoid tyramine-containing foods and supplements. Avoid food containing high amounts of tyramine (>100mg). Tyramine-containing foods include cheese, red wine, flava beans, pickled food, cured food, and alcoholic beverages.
- Take with or without food. The absorption is unaffected by food.
Products
Purchasing individual compounds or compound libraries for your research?
Learn More- Product Images
- International/Other Brands
- Antizolid (Verisfield) / Linosept (Orion) / Linozid (Orion) / Lizbid (Abbott) / Lizemox (Molekule) / Lizolid (Glenmark) / Xolid (Corona) / Zenix (Hemofarm) / Zizolid (Biofarma) / Zodlin (FDC) / Zolinid (Teva) / Zyvoxid (Pfizer)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataLinezolid Injection, solution 2 mg/1mL Intravenous Hospira, Inc. 2015-06-18 Not applicable US 
Linezolid Tablet 600 mg Oral Panda Pharmaceuticals Inc. Not applicable Not applicable Canada 
Linezolid Injection Solution Intravenous Jamp Pharma Corporation 2019-12-30 Not applicable Canada Linezolid Injection Solution Intravenous Hospira Healthcare Ulc Not applicable Not applicable Canada Linezolid Injection Solution Intravenous TEVA Canada Limited 2014-08-18 2018-05-17 Canada Linezolid Injection Solution Intravenous Neo Health Canada Inc. Not applicable Not applicable Canada Linezolid Injection Solution Intravenous Auro Pharma Inc Not applicable Not applicable Canada Linezolid Injection Solution Intravenous Sandoz Canada Incorporated Not applicable Not applicable Canada Linezolid Injection Solution Intravenous Mda Inc. Not applicable Not applicable Canada Linezolid Injection Solution Intravenous Fresenius Kabi 2015-06-12 Not applicable Canada Additional Data Available- Application NumberApplication NumberAvailable for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct CodeAvailable for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataApo-linezolid Tablet Oral Apotex Corporation 2014-08-19 Not applicable Canada Linezolid Tablet, film coated 600 mg/1 Oral Apotex Corp. 2015-06-22 2018-11-30 US Linezolid Suspension 100 mg/5mL Oral Greenstone LLC 2015-05-18 Not applicable US Linezolid Powder, for suspension 100 mg/5mL Oral West-Ward Pharmaceuticals Corp. 2015-06-03 Not applicable US Linezolid Injection, solution 600 mg/300mL Intravenous Mylan Institutional 2018-07-31 Not applicable US Linezolid Tablet, film coated 600 mg/1 Oral Camber Pharmaceuticals, Inc. 2015-12-21 Not applicable US Linezolid Tablet, film coated 600 mg/1 Oral Alembic Pharmaceuticals Inc. 2015-12-22 Not applicable US Linezolid Injection, solution 600 mg/300mL Intravenous AuroMedics Pharma LLC 2016-08-04 Not applicable US Linezolid Injection, solution 600 mg/300mL Intravenous Sun Pharmaceutical Industries, Inc. 2017-02-01 Not applicable US Linezolid Injection, solution 2 mg/1mL Intravenous Fresenius Kabi Norge As 2017-07-27 Not applicable US Additional Data Available- Application NumberApplication NumberAvailable for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct CodeAvailable for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories
- ATC Codes
- J01XX08 — Linezolid
- Drug Categories
- Acetamides
- Acetates
- Acids, Acyclic
- Agents that produce hypertension
- Agents that reduce seizure threshold
- Amides
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antibacterials for Systemic Use
- Antidepressive Agents
- Antiinfectives for Systemic Use
- Central Nervous System Depressants
- Enzyme Inhibitors
- Fatty Acids
- Fatty Acids, Volatile
- Immunosuppressive Agents
- Lipids
- Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates
- Monoamine Oxidase Inhibitors
- Myelosuppressive Agents
- Oxazoles
- Oxazolidinone Antibacterial
- Oxazolidinones
- Protein Synthesis Inhibitors
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin Modulators
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Oxazinanes
- Sub Class
- Morpholines
- Direct Parent
- Phenylmorpholines
- Alternative Parents
- Aniline and substituted anilines / Dialkylarylamines / Fluorobenzenes / Oxazolidinones / Aryl fluorides / Acetamides / Carbamate esters / Secondary carboxylic acid amides / Organic carbonic acids and derivatives / Dialkyl ethers show 7 more
- Substituents
- Acetamide / Amine / Amino acid or derivatives / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carbamic acid ester show 26 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- organofluorine compound, acetamides, morpholines, oxazolidinone (CHEBI:63607)
Chemical Identifiers
- UNII
- ISQ9I6J12J
- CAS number
- 165800-03-3
- InChI Key
- TYZROVQLWOKYKF-ZDUSSCGKSA-N
- InChI
- InChI=1S/C16H20FN3O4/c1-11(21)18-9-13-10-20(16(22)24-13)12-2-3-15(14(17)8-12)19-4-6-23-7-5-19/h2-3,8,13H,4-7,9-10H2,1H3,(H,18,21)/t13-/m0/s1
- IUPAC Name
- N-{[(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
- SMILES
- CC(=O)NC[[email protected]]1CN(C(=O)O1)C1=CC(F)=C(C=C1)N1CCOCC1
References
- Synthesis Reference
- US5688792
- General References
- Park IN, Hong SB, Oh YM, Kim MN, Lim CM, Lee SD, Koh Y, Kim WS, Kim DS, Kim WD, Shim TS: Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. J Antimicrob Chemother. 2006 Sep;58(3):701-4. Epub 2006 Jul 19. [PubMed:16857689]
- External Links
- Human Metabolome Database
- HMDB0014739
- KEGG Drug
- D00947
- KEGG Compound
- C08146
- PubChem Compound
- 441401
- PubChem Substance
- 46504452
- ChemSpider
- 390139
- BindingDB
- 50116067
- 190376
- ChEBI
- 63607
- ChEMBL
- CHEMBL126
- ZINC
- ZINC000002008866
- Therapeutic Targets Database
- DAP000398
- PharmGKB
- PA450233
- PDBe Ligand
- ZLD
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Linezolid
- AHFS Codes
- 08:12.28.24 — Oxazolidinones
- PDB Entries
- 3cpw / 3dll / 4k7q / 4wfa / 5nz0
- FDA label
- Download (106 KB)
- MSDS
- Download (43.7 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Diabetes Mellitus 1 4 Completed Treatment Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Treatment Infections, Gram-Positive Bacterial / Skin and Connective Tissue Diseases 1 4 Completed Treatment Methicillin Resistant Staphylococcus Aureus (MRSA) 1 4 Completed Treatment Methicillin Resistant Staphylococcus Aureus (MRSA) / Skin/Soft Tissue Infections 1 4 Completed Treatment Methicillin-Resistant Staphylococcus Aureus (MRSA) 1 4 Completed Treatment MRSA Infection 1 4 Completed Treatment Ventilator-associated Bacterial Pneumonia / Ventilator-Associated Pneumonia (VAP) 1 4 Recruiting Treatment Illness, Critical / Mechanical Ventilation Complication 1 4 Terminated Prevention Acute acute bacterial skin and skin structure infections / Bacteremia / Endocarditis / Health Care Associated Pneumonia / Osteomyelitis/Septic Arthritis 1
Pharmacoeconomics
- Manufacturers
- Pharmacia and upjohn co
- Packagers
- Fresenius Kabi AB
- Lake Erie Medical and Surgical Supply
- Murfreesboro Pharmaceutical Nursing Supply
- Pfizer Inc.
- Pharmacia Inc.
- Dosage Forms
Form Route Strength Tablet Oral 600 mg Injection Intravenous Tablet, coated Oral 600 mg Injection, solution Intravenous 2 mg/1mL Injection, solution Intravenous 200 mg/100mL Injection, solution Intravenous 600 mg/300mL Powder Not applicable 1 kg/1kg Powder, for suspension Oral 100 mg/5mL Tablet Oral 600 mg/1 Tablet, film coated Oral 600 MG Solution Parenteral 2 mg/ml Injection, solution Parenteral 2 MG/ML Injection Intravenous 2 mg/ml Tablet, delayed release Oral 600 mg Solution Intravenous 2 mg Solution Intravenous 2 mg/mL Injection, solution Intravenous 2 mg/ml Solution Intravenous 600 mg Tablet, film coated Oral 400 mg Solution Intravenous 200 mg Injection Intravenous 600 mg/300mL Injection, solution Intravenous 400 mg/200mL Suspension Oral 100 mg/5mL Tablet, film coated Oral Tablet, film coated Oral 400 mg/1 Tablet, film coated Oral 600 mg/1 Granule Oral 20 MG/ML For solution Intravenous 600 MG/300ML Powder, for suspension Oral Solution Intravenous Tablet Oral Injection, solution 2 MG/ML Granule, for suspension Oral 100 mg/5ml Granule Oral 100 MG/5ML - Prices
Unit description Cost Unit Zyvox 600 mg tablet 93.81USD tablet Zyvox 200 mg/100 ml iv soln 0.6USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region Unlock Additional DataUS5688792 No 1997-11-18 2014-11-18 US CA2168560 No 2001-08-14 2014-08-16 Canada US6559305 Yes 2003-05-06 2021-07-29 US US6514529 Yes 2003-02-04 2021-09-15 US Additional Data Available- Filed OnFiled OnAvailable for Purchase
The date on which a patent was filed with the relevant government.
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Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 3 mg/mL Not Available logP 0.9 Not Available - Predicted Properties
Property Value Source Water Solubility 1.44 mg/mL ALOGPS logP 0.61 ALOGPS logP 0.64 ChemAxon logS -2.4 ALOGPS pKa (Strongest Acidic) 14.45 ChemAxon pKa (Strongest Basic) -0.66 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 71.11 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 84.47 m3·mol-1 ChemAxon Polarizability 34.06 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 No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9363 Caco-2 permeable + 0.8866 P-glycoprotein substrate Substrate 0.5881 P-glycoprotein inhibitor I Inhibitor 0.7599 P-glycoprotein inhibitor II Non-inhibitor 0.6478 Renal organic cation transporter Non-inhibitor 0.7469 CYP450 2C9 substrate Non-substrate 0.7898 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.5904 CYP450 1A2 substrate Non-inhibitor 0.7811 CYP450 2C9 inhibitor Non-inhibitor 0.8174 CYP450 2D6 inhibitor Non-inhibitor 0.8112 CYP450 2C19 inhibitor Non-inhibitor 0.5664 CYP450 3A4 inhibitor Non-inhibitor 0.7563 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5544 Ames test Non AMES toxic 0.6839 Carcinogenicity Non-carcinogens 0.8916 Biodegradation Not ready biodegradable 0.9895 Rat acute toxicity 2.4938 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7883 hERG inhibition (predictor II) Inhibitor 0.6297
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
Yes
Inhibitor
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
- Sinclair A, Arnold C, Woodford N: Rapid detection and estimation by pyrosequencing of 23S rRNA genes with a single nucleotide polymorphism conferring linezolid resistance in Enterococci. Antimicrob Agents Chemother. 2003 Nov;47(11):3620-2. [PubMed:14576130]
- Meka VG, Pillai SK, Sakoulas G, Wennersten C, Venkataraman L, DeGirolami PC, Eliopoulos GM, Moellering RC Jr, Gold HS: Linezolid resistance in sequential Staphylococcus aureus isolates associated with a T2500A mutation in the 23S rRNA gene and loss of a single copy of rRNA. J Infect Dis. 2004 Jul 15;190(2):311-7. Epub 2004 Jun 9. [PubMed:15216466]
- Zhu W, Tenover FC, Limor J, Lonsway D, Prince D, Dunne WM Jr, Patel JB: Use of pyrosequencing to identify point mutations in domain V of 23S rRNA genes of linezolid-resistant Staphylococcus aureus and Staphylococcus epidermidis. Eur J Clin Microbiol Infect Dis. 2007 Mar;26(3):161-5. [PubMed:17393201]
- Colca JR, McDonald WG, Waldon DJ, Thomasco LM, Gadwood RC, Lund ET, Cavey GS, Mathews WR, Adams LD, Cecil ET, Pearson JD, Bock JH, Mott JE, Shinabarger DL, Xiong L, Mankin AS: Cross-linking in the living cell locates the site of action of oxazolidinone antibiotics. J Biol Chem. 2003 Jun 13;278(24):21972-9. Epub 2003 Apr 10. [PubMed:12690106]
- Feng J, Lupien A, Gingras H, Wasserscheid J, Dewar K, Legare D, Ouellette M: Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance. Genome Res. 2009 Jul;19(7):1214-23. doi: 10.1101/gr.089342.108. Epub 2009 Apr 6. [PubMed:19351617]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
References
- Stevens DL, Dotter B, Madaras-Kelly K: A review of linezolid: the first oxazolidinone antibiotic. Expert Rev Anti Infect Ther. 2004 Feb;2(1):51-9. [PubMed:15482171]
- Taylor JJ, Wilson JW, Estes LL: Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006 Jul 15;43(2):180-7. Epub 2006 Jun 9. [PubMed:16779744]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Primary amine oxidase activity
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOB
- Uniprot ID
- P27338
- Uniprot Name
- Amine oxidase [flavin-containing] B
- Molecular Weight
- 58762.475 Da
References
- Stevens DL, Dotter B, Madaras-Kelly K: A review of linezolid: the first oxazolidinone antibiotic. Expert Rev Anti Infect Ther. 2004 Feb;2(1):51-9. [PubMed:15482171]
- Taylor JJ, Wilson JW, Estes LL: Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006 Jul 15;43(2):180-7. Epub 2006 Jun 9. [PubMed:16779744]
Drug created on June 13, 2005 07:24 / Updated on November 30, 2020 13:38
