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药品详细

Linezolid (利奈唑胺 )

化学结构式图
中文名
利奈唑胺
英文名
Linezolid
分子式
Not Available
化学名
N-{[(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
分子量
Average: 337.3461
Monoisotopic: 337.143784348
CAS号
165800-03-3
ATC分类
J01X Other Antibacterials
药物类型
small molecule
阶段
商品名
Linezlid;Zyvox;Zyvoxid;
同义名
linezolid;
基本介绍

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.

生产厂家
  • Pharmacia and upjohn co
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Link
  2. 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
剂型
Form Route Strength
Solution Intravenous
Tablet Oral
规格
Unit description Cost Unit
Zyvox 600 mg tablet 93.81 USD tablet
Zyvox 200 mg/100 ml iv soln 0.6 USD ml
化合物类型
Type small molecule
Classes
  • Carbamates and Derivatives
  • Benzene and Derivatives
  • Halobenzenes
  • Morpholines
  • Oxazolidinones
  • Anilines
Substructures
  • Carbamates and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Morpholines
  • Oxazolidinones
  • Aryl Halides
  • Anilines
适应症
antibacterials 抗细菌;
药理
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.
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.
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
Route of elimination Not Available
Half life 4.5-5.5 hours
Clearance Not Available
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
理化性质
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility 3 mg/mL PhysProp
logP 0.9 PhysProp
Predicted Properties
Property Value Source
water solubility 1.44e+00 g/l ALOGPS
logP 0.61 ALOGPS
logP 0.64 ChemAxon Molconvert
logS -2.37 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 71.11 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 84.47 ChemAxon Molconvert
polarizability 34.06 ChemAxon Molconvert
药物相互作用
Drug Interaction
Citalopram Combination associated with possible serotoninergic syndrome
Desvenlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
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 Linezolide, a MAO inhibitor, may increase the serotonergic effect of fluoxetine, a SSRI. Increased for of serotonin syndrome. Concomitant therapy should be avoided.
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
Tetrabenazine Tetrabenazine may increase the adverse/toxic effects of Linezolid. Concomitant therapy is contraindicated.
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.
Tramadol Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Linezolid.
Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the adverse effects of Linezolid. These agents should not be administered within 14 days of each other.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin 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.
Venlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
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.
食物相互作用
  • Take without regard to meals.

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