QuickView for Linezolid (compound)

Summary
General Info

PubChem

PubChem Compound 3929

Name:	linezolid
PubChem Compound ID:	3929
Molecular formula:	C₁₆H₂₀FN₃O₄
Molecular weight:	337.346 g/mol
Synonyms:	A4091/0174440

DrugBank

Identification

Name:	linezolid
Name (isomeric):	DB00601
Drug Type:	small molecule
Brand:	Zyvoxid, Zyvox, Linezlid
Category:	Protein Synthesis Inhibitors, Anti-Infective Agents, Antibacterial Agents
CAS number:	165800-03-3

Pharmacology

Indication:	For the treatment of bacterial infections caused by susceptible strains of vancomycin resistant <i>Enterococcus faecium</i>, <i>Staphylococcal aureus</i> (methicillin resistant and susceptible strains), <i>Streptococcus pneumoniae</i>, <i>Streptococcus pyogenes</i>, <i>Streptococcus agalactiae</i>.
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 methicil... show more » 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. show less «
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 f... show more » 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. show less «
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%.
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
Toxicity:	Clinical signs of acute toxicity lead to decreased activity, ataxia, vomiting and tremors.
Affected organisms:	Gram negative and gram positive bacteria

Interactions

Food interaction:

Take without regard to meals.

Drug interaction:

Dobutamine	Possible increase of arterial pressure
Fenoterol	Possible increase of arterial pressure
Norepinephrine	Possible increase of arterial pressure
Procaterol	Possible increase of arterial pressure
Brimonidine	MAO Inhibitors like linezolid may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.

Dobutamine	Possible increase of arterial pressure
Fenoterol	Possible increase of arterial pressure
Norepinephrine	Possible increase of arterial pressure
Procaterol	Possible increase of arterial pressure
Brimonidine	MAO Inhibitors like linezolid may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.
Phenylephrine	Possible increase of arterial pressure
Metaraminol	Possible increase of arterial pressure
Orciprenaline	Possible increase of arterial pressure
Tolcapone	Tolcapone and Linezolid decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
Citalopram	Combination associated with possible serotoninergic syndrome
Escitalopram	Combination associated with possible serotoninergic syndrome
Trimipramine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Ephedrine	Possible increase of arterial pressure
Paroxetine	Combination associated with possible serotoninergic syndrome
Pseudoephedrine	Possible increase of arterial pressure
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Fluoxetine	Linezolide, a MAO inhibitor, may increase the serotonergic effect of fluoxetine, a SSRI. Increased for of serotonin syndrome. Concomitant therapy should be avoided.
Buprenorphine	Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like linezolid. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Epinephrine	Possible increase of arterial pressure
Tranylcypromine	The MAO inhibitor, Tranylcypromine, may increase the adverse effects of Linezolid. These agents should not be administered within 14 days of each other.
Isoproterenol	Possible increase of arterial pressure
Mephentermine	Possible increase of arterial pressure
Methoxamine	Possible increase of arterial pressure
Ephedra	Possible increase of arterial pressure
Fluvoxamine	Combination associated with possible serotoninergic syndrome
Sertraline	Combination associated with possible serotoninergic syndrome
Tetrabenazine	Tetrabenazine may increase the adverse/toxic effects of Linezolid. Concomitant therapy is contraindicated.
Nefazodone	Combination associated with possible serotoninergic syndrome
Pirbuterol	Possible increase of arterial pressure
Bezafibrate	MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like linezolid.
Zolmitriptan	The MAO inhibitor, linezolid, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing linezolid are contraindicated.
Vilazodone	MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.
Desvenlafaxine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Tramadol	Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Linezolid.
Terbutaline	Possible increase of arterial pressure
Phenylpropanolamine	Possible increase of arterial pressure
Salbutamol	Possible increase of arterial pressure
Dopamine	Possible increase of arterial pressure
Venlafaxine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

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Targets

23S rRNA

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.

Actions:

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.
View Article

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.
View Article

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.
View Article

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.
View Article

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.
View Article

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.
View Article

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. Epub 2009 Apr 6.
View Article

Enzymes

Amine oxidase [flavin-containing] A

Amine oxidase [flavin-containing] B