| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:07:45 |
| Primary Accession Number |
DB00601 |
| Secondary Accession Number |
|
| Name |
Linezolid |
| Drug Type |
- Approved
- Investigational
- Small Molecule
|
| 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. |
| Synonyms |
- linezolid
|
| Brand Names |
- Linezlid
- Zyvox
- Zyvoxid
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
N-[[(5S)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide |
| Chemical Formula |
C16H20FN3O4 |
| Chemical Structure |
 |
| CAS Registry Number |
165800-03-3 |
| InChI Identifier |
InChI=1/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/f/h18H |
| InChI Key |
TYZROVQLWOKYKF-XCXMHTFKDR |
| KEGG Drug |
D00947  |
| KEGG Compound |
C08146  |
| PubChem Compound |
441401  |
| PubChem Substance |
10346  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA450233  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02243684  |
| RxList Link |
http://www.rxlist.com/cgi/generic3/linezolid.htm  |
| PDRhealth Link |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zyv1556.shtml  |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Linezolid  |
| FDA Label |
|
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
Not Available |
| Average Molecular Weight |
337.3461 |
| Monoisotopic Molecular Weight |
337.1438 |
| State |
Solid |
| Melting Point |
Not Available |
| Experimental Water Solubility |
3 mg/mL
Source: PhysProp
|
| Predicted Water Solubility |
1.44e+00 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
0.9
Source: PhysProp
|
| Predicted LogP |
0.61
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-2.37
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
CC(=O)NC[C@H]1CN(C(=O)O1)C1=CC(F)=C(C=C1)N1CCOCC1 |
| Canonical SMILES |
CC(=O)NCC1CN(C(=O)O1)C1=CC(F)=C(C=C1)N1CCOCC1 |
| Drug Category |
- Anti-Infective Agents
- Antibacterial Agents
- Protein Synthesis Inhibitors
|
| ATC Codes |
|
| AHFS Codes |
|
| 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. |
| Pharmacology |
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. |
| 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%. |
| Toxicity |
Clinical signs of acute toxicity lead to decreased activity, ataxia, vomiting and tremors. |
| Protein Binding |
31% |
| Biotransformation |
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 |
| Half Life |
4.5-5.5 hours |
| Dosage Forms |
| Form |
Route |
| Solution |
Intravenous |
| Tablet |
Oral |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
| Drug |
Interaction |
| Citalopram |
Combination associated with possible serotoninergic syndrome |
| Dobutamine |
Possible increase of arterial pressure |
| Dopamine |
Possible increase of arterial pressure |
| Ephedra |
Possible increase of arterial pressure |
| Ephedrine |
Possible increase of arterial pressure |
| Epinephrine |
Possible increase of arterial pressure |
| Escitalopram |
Combination associated with possible serotoninergic syndrome |
| Fenoterol |
Possible increase of arterial pressure |
| Fluoxetine |
Possible increase of arterial pressure |
| Fluvoxamine |
Combination associated with possible serotoninergic syndrome |
| Isoproterenol |
Possible increase of arterial pressure |
| Mephentermine |
Possible increase of arterial pressure |
| Metaraminol |
Possible increase of arterial pressure |
| Methoxamine |
Possible increase of arterial pressure |
| Nefazodone |
Combination associated with possible serotoninergic syndrome |
| Norepinephrine |
Possible increase of arterial pressure |
| Orciprenaline |
Possible increase of arterial pressure |
| Paroxetine |
Combination associated with possible serotoninergic syndrome |
| Phenylephrine |
Possible increase of arterial pressure |
| Phenylpropanolamine |
Possible increase of arterial pressure |
| Pirbuterol |
Possible increase of arterial pressure |
| Procaterol |
Possible increase of arterial pressure |
| Pseudoephedrine |
Possible increase of arterial pressure |
| Salbutamol |
Possible increase of arterial pressure |
| Sertraline |
Combination associated with possible serotoninergic syndrome |
| Terbutaline |
Possible increase of arterial pressure |
| Venlafaxine |
Combination associated with possible serotoninergic syndrome |
|
| Food Interactions |
- Take without regard to meals.
|
| Pathways |
Not Available
|
| 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
]
- http://home.intekom.com/pharm/pharmaca/zyvoxid.html
- Wikipedia

- RxList

- PDRhealth

|
| Organisms Affected |
- Gram negative and gram positive bacteria
|
| Phase 1 Metabolizing Enzymes |
- Monoamine oxidase type A (MAO-A)
|
| Targets |
- 23S rRNA
|
|
Drug Target 1
[top]
|
| Target 1 ID |
884 |
| Target 1 Name |
23S rRNA |
| Target 1 Synonyms |
- 23S ribosomal ribonucleic acid
|
| Target 1 Gene Name |
Not Available |
| Target 1 Protein Sequence |
Not Available |
| Target 1 Number of Residues |
0 |
| Target 1 Molecular Weight |
Not Available |
| Target 1 Theoretical pI |
Not Available |
| Target 1 GO Classification |
|
Function
|
transferase activity
translation
RNA binding
|
|
Process
|
rRNA processing
RNA processing and modification
|
|
Component
|
| cell |
|
| Target 1 General Function |
Translation, ribosomal structure and biogenesis |
| Target 1 Specific Function |
In prokaryotes, the 23S rRNA is part of the large subunit (the 50S) that joins with the 30S small subunit to create the functional 70S ribosome. The ribosome is comprised of 3 RNAs: the 23S, the 16S and the 5S ribosomal RNAs. The 23S and the 5S associate with their respective proteins to make up the large subunit of the ribosome, while the 16S RNA associates with its proteins to make up the small subunit. |
| Target 1 Pathways |
| Name |
SMPDB Link |
KEGG Link |
| Ribosome |
|
map03010  |
|
| Target 1 Reactions |
- tRNA-aminoacid + ATP + polypeptide(n) = polypeptide(n+1) + ADP
|
| Target 1 Pfam Domain Function |
Not Available |
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Essential |
| Target 1 GenBank ID Protein |
Not Available |
| Target 1 UniProtKB/Swiss-Prot ID |
Not Available |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
Not Available |
| Target 1 PDB ID |
1EMI  |
| Target 1 PDB File |
Show |
| Target 1 3D Structure |
|
| Target 1 Cellular Location |
|
| Target 1 Gene Sequence |
>23S rRNA sequence
GATTAAGTTATTAAGGGCGCACGGTGGATGCCTTGGCACTAGAAGCCGATGAAGGACGTT
ACTAACGACGATATGCTTTGGGGAGCTGTAAGTAAGCTTTGATCCAGAGATTTCCGAATG
GGGAAACCCAGCATGAGTTATGTCATGTTATCGATATGTGAATACATAGCATATCAGAAG
GCACACCCGGAGAACTGAAACATCTTAGTACCCGGAGGAAGAGAAAGAAAATTCGATTCC
CTTAGTAGCGGCGAGCGAAATGGGAAGAGCCCAAACCAACAAGCTTGCTTGTTGGGGTTG
TAGGACACTCTATACGGAGTTACAAAGGACGACATTAGACGAATCATCTGGAAAGATGAA
TCAAAGAAGGTAATAATCCTGTAGTCGAAAATGTTGTCTCTCTTGAGTGGATCCTGAGTA
CGACGGAGCACGTGAAATTCCGTCGGAATCTGGGAGGACCATCTCCTAAGGCTAAATACT
CTCTAGTGACCGATAGTGAACCAGTACCGTGAGGGAAAGGTGAAAAGCACCCCGGAAGGG
GAGTGAAATAGAACCTGAAACCGTGTGCTTACAAGTAGTCAGAGCCCGTTAATGGGTGAT
GGCGTGCCTTTTGTAGAATGAACCGGCGAGTTACGATTTGATGCAAGGTTAAGCAGTAAA
TGTGGAGCCGTAGCGAAAGCGAGTCTGAATAGGGCGTTTAGTATTTGGTCGTAGACCCGA
AACCAGGTGATCTACCCTTGGTCAGGTTGAAGTTCAGGTAACACTGAATGGAGGACCGAA
CCGACTTACGTTGAAAAGTGAGCGGATGAACTGAGGGTAGCGGAGAAATTCCAATCGAAC
CTGGAGATAGCTGGTTCTCTCCGAAATAGCTTTAGGGCTAGCCTCAAGTGATGATTATTG
GAGGTAGAGCACTGTTTGGACGAGGGGCCCCTCTCGGGTTACCGAATTCAGACAAACTCC
GAATGCCAATTAATTTAACTTGGGAGTCAGAACATGGGTGATAAGGTCCGTGTTCGAAAG
GGAAACAGCCCAGACCACCAGCTAAGGTCCCAAAATATATGTTAAGTGGAAAAGGATGTG
GCGTTGCCCAGACAACTAGGATGTTGGCTTAGAAGCAGCCATCATTTAAAGAGTGCGTAA
TAGCTCACTAGTCGAGTGACACTGCGCCGAAAATGTACCGGGGCTAAACATATTACCGAA
GCTGTGGATTGTCCTTTGGACAATGGTAGGAGAGCGTTCTAAGGGCGTTGAAGCATGATC
GTAAGGACATGTGGAGCGCTTAGAAGTGAGAATGCCGGTGTGAGTAGCGAAAGACGGGTG
AGAATCCCGTCCACCGATTGACTAAGGTTTCCAGAGGAAGGCTCGTCCGCTCTGGGTTAG
TCGGGTCCTAAGCTGAGGCCGACAGGCGTAGGCGATGGATAACAGGTTGATATTCCTGTA
CCACCTATAATCGTTTTAATCGATGGGGGGACGCAGTAGGATAGGCGAAGCGTGCGATTG
GATTGCACGTCTAAGCAGTAAGGCTGAGTATTAGGCAAATCCGGTACTCGTTAAGGCTGA
GCTGTGATGGGGAGAAGACATTGTGTCTTCGAGTCGTTGATTTCACACTGCCGAGAAAAG
CCTCTAGATAGAAAATAGGTGCCCGTACCGCAAACCGACACAGGTAGTCAAGATGAGAAT
TCTAAGGTGAGCGAGCGAACTCTCGTTAAGGAACTCGGCAAAATGACCCCGTAACTTCGG
GAGAAGGGGTGCTCTTTAGGGTTAACGCCCAGAAGAGCCGCAGTGAATAGGCCCAAGCGA
CTGTTTATCAAAAACACAGGTCTCTGCTAAACCGTAAGGTGATGTATAGGGGCTGACGCC
TGCCCGGTGCTGGAAGGTTAAGAGGAGTGGTTAGCTTCTGCGAAGCTACGAATCGAAGCC
CCAGTAAACGGCGGCCGTAACTATAACGGTCCTAAGGTAGCGAAATTCCTTGTCGGGTAA
GTTCCGACCCGCACGAAAGGCGTAACGATTTGGGCACTGTCTCAACGAGAGACTCGGTGA
AATCATAGTACCTGTGAAGATGCAGGTTACCCGCGACAGGACGGAAAGACCCCGTGGAGC
TTTACTGTAGCCTGATATTGAAATTCGGCACAGCTTGTACAGGATAGGTAGGAGCCTTTG
AAACGTGAGCGCTAGCTTACGTGGAGGCGCTGGTGGGATACTACCCTAGCTGTGTTGGCT
TTCTAACCCGCACCACTTATCGTGGTGGGAGACAGTGTCAGGCGGGCAGTTTGACTGGGG
CGGTCGCCTCCTAAAAGGTAACGGAGGCGCTCAAAGGTTCCCTCAGAATGGTTGGAAATC
ATTCATAGAGTGTAAAGGCATAAGGGAGCTTGACTGCGAGACCTACAAGTCGAGCAGGGT
CGAAAGACGGACTTAGTGATCCGGTGGTTCCGCATGGAAGGGCCATCGCTCAACGGATAA
AAGCTACCCCGGGGATAACAGGCTTATCTCCCCCAAGAGTTCACATCGACGGGGAGGTTT
GGCACCTCGATGTCGGCTCATCGCATCCTGGGGCTGTAGTCGGTCCCAAGGGTTGGGCTG
TTCGCCCATTAAAGCGGTACGCGAGCTGGGTTCAGAACGTCGTGAGACAGTTCGGTCCCT
ATCCGTCGTGGGCGTAGGAAATTTGAGAGGAGCTGTCCTTAGTACGAGAGGACCGGGATG
GACATACCTCTGGTGTACCAGTTGTCGTGCCAACGGCATAGCTGGGTAGCTATGTGTGGA
CGGGATAAGTGCTGAAAGCATCTAAGCATGAAGCCCCCCTCAAGATGAGATTTCCCAACT
TCGGTTATAAGATCCCTCAAAGATGATGAGGTTAATAGGTTCGAGGTGGAAGCATGGTGA
CATGTGGAGCTGACGAATACTAATCGATCGAAGACTTAATCAA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
Not Available |
| Target 1 GenAtlas ID |
Not Available |
| Target 1 HGNC ID |
Not Available |
| Target 1 Chromosome Location |
Not Available |
| Target 1 Locus |
Not Available |
| Target 1 SNPs |
Not Available |
| Target 1 General References |
- Barrett JF: Linezolid Pharmacia Corp. Curr Opin Investig Drugs. 2000 Oct;1(2):181-7. [PubMed
]
|
| Target 1 Drug References |
- 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
]
- 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
]
- 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
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
- 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
]
|