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リネゾリド

リネゾリド 化学構造式
165800-03-3
CAS番号.
165800-03-3
化学名:
リネゾリド
别名:
リネゾリド;リネゾリド (JAN)
英語化学名:
Linezolid
英語别名:
Zyvox;Linox;Zyvoxid;U 100766;Linospan;LINEZOLID;LINEZOLIDE;PNU 100766;Ray Nizzoli;Linezolid API
CBNumber:
CB1287912
化学式:
C16H20FN3O4
分子量:
337.35
MOL File:
165800-03-3.mol

リネゾリド 物理性質

融点 :
176-1780C
比旋光度 :
D20 -9° (c = 0.919 in chloroform)
貯蔵温度 :
Store at RT
溶解性:
DMSO: >20mg/mL
外見 :
powder
色:
white to off-white
InChIKey:
TYZROVQLWOKYKF-ZDUSSCGKSA-N
CAS データベース:
165800-03-3(CAS DataBase Reference)
安全性情報
  • リスクと安全性に関する声明
  • 危険有害性情報のコード(GHS)
主な危険性  Xn
Rフレーズ  20/21/22
Sフレーズ  36-24/25
WGK Germany  3
RTECS 番号 AC2720000
HSコード  29419000
有毒物質データの 165800-03-3(Hazardous Substances Data)
絵表示(GHS)
注意喚起語 Danger
危険有害性情報
コード 危険有害性情報 危険有害性クラス 区分 注意喚起語 シンボル P コード
H372 長期にわたる、または反復暴露により臓器の障 害 特定標的臓器有害性、単回暴露 1 危険 P260, P264, P270, P314, P501
注意書き
P260 粉じん/煙/ガス/ミスト/蒸気/スプレーを吸入しないこ と。
P314 気分が悪い時は、医師の診断/手当てを受けること。

リネゾリド 価格 もっと(16)

メーカー 製品番号 製品説明 CAS番号 包装 価格 更新時間 購入
富士フイルム和光純薬株式会社(wako) W01FLC227724
(S)-N-((3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide
165800-03-3 1g ¥9200 2018-12-26 購入
富士フイルム和光純薬株式会社(wako) W01FLC227724
(S)-N-((3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide
165800-03-3 5g ¥27700 2018-12-26 購入
Sigma-Aldrich Japan PHR1885 リネゾリド Pharmaceutical Secondary Standard; Certified Reference Material
Linezolid Pharmaceutical Secondary Standard; Certified Reference Material
165800-03-3 500mg ¥31900 2018-12-25 購入
Sigma-Aldrich Japan 1367561 リネゾリド United States Pharmacopeia (USP) Reference Standard
Linezolid United States Pharmacopeia (USP) Reference Standard
165800-03-3 200mg ¥70900 2018-12-25 購入
富士フイルム和光純薬株式会社(wako) W01USP1367561 リネゾリド
Linezolid
165800-03-3 200mg ¥73500 2018-12-26 購入

リネゾリド MSDS


Linezolid

リネゾリド 化学特性,用途語,生産方法

外観

白色~わずかにうすい黄色, 結晶性粉末~粉末

溶解性

メタノールに可溶

用途

リネゾリド (linezolid) は抗生物質の一種で、バンコマイシンに対する薬剤耐性を獲得したバンコマイシン耐性腸球菌(Vancomycin-resistant Enterococci, VRE)および黄色ブドウ球菌 (Vancomycin-resistant Staphylococcus aureus, VRSA) に有効な新薬として登場した。オキサゾリジノン系合成抗菌剤という新系統の抗生物質であり。 リンコサミド系(クリンダマイシン)、ストレプトグラミン系と抗菌活性機序および抗菌スペクトルが類似しているため、同じグループに分類される。 リボソームの50Sサブユニットに結合して70S開始複合体の形成を阻害することにより、細菌の蛋白合成が阻害され、菌の増殖を抑制する。

用途

オキサゾリジノン系抗菌剤で す。細菌リボソーム 50S に結合し、タンパ ク質合成を阻害します。リボソーム伸長反応、 ペプチド結合の合成は阻害しません。バンコ マイシン耐性腸球菌(VRE)及びメチシリン 耐性黄色球菌(MRSA)に対して、抗菌作用 を示します。

用途

オキサゾリジノン系抗生物質です。細菌のポリペプチド鎖伸長開始前のタンパク質合成を阻害 します。

効能

抗菌薬, タンパク質合成阻害薬

商品名

ザイボックス (ファイザー); ザイボックス (ファイザー); リネゾリド (光製薬)

説明

Linezolid reached the US market for the treatment of patients with infections caused by serious Gram-positive pathogens, particularly skin and soft tissue infections, communityacquired pneumonia and vancomycin-resistant enterococcal infections. Linezolid is the (S)-enantiomer of an oxazolidin-2-one synthesized in a multistep process from 3,4- difluoronitrobenzene, the key step being the cyclization of a carbamate, using a chiral epoxyester, into an enantiomerically pure oxazolidin-2-one. Linezolid can be considered as the first of a new class of antibacterial agents known as oxazolidinones, its mechanism of action being related to the inhibition of early ribosomal protein synthesis without directly inhibiting DNA or RNA synthesis. In vitro studies demonstrated that linezolid was effective, at potency levels similar to vancomycin, against staphylococcal, streptococcal and pneumococcal infections (MIC values in the range of 0.5 to 2 μg/ml), enterococcal species including VRE and VSE (MIC values about 4 μg/ml), but also other vancomycin-resistant bacteria. Linezolid is rapidly absorbed orally, its bioavailability is nearly complete at 250 mg dose giving a Cmax to MIC ratio sufficient to have pathogenic strain eradication in the clinical setting. It is considered that this new promising agent may offer new options for therapy of multi-drug infections.

化学的特性

White Solid

Originator

Pharmacia Corp. (US)

使用

Prototype of the oxazolidinone antimicrobials; inhibits bacterial mRNA translation.

使用

antibacterial

定義

ChEBI: An organofluorine compound that consists of 1,3-oxazolidin-2-one bearing an N-3-fluoro-4-(morpholin-4-yl)phenyl group as well as an acetamidomethyl group at position 5. A synthetic antibacterial agent that inhibits bacterial protein synt esis by binding to a site on 23S ribosomal RNA of the 50S subunit and prevents further formation of a functional 70S initiation complex.

brand name

Zyvox (Pharmacia & Upjohn).

抗菌性

It exhibits potent activity against a wide range of Gram-positive organisms, including those that are resistant to other antimicrobial agents. Methicillinresistant Staph. aureus and coagulase-negative staphylococci are susceptible, as are enterococci, including vancomycin-resistant Enterococcus faecalis and Ent. faecium. Penicillin-sensitive and resistant isolates of Streptococcus pneumoniae are equally susceptible. Less common Gram-positive pathogens are also susceptible; the minimum inhibitory concentrations (MICs) for Bacillus spp., Corynebacterium spp., Listeria monocytogenes, Aerococcus spp., Micrococcus spp. and Rhodococcus equi are all ≤2 mg/L. M. tuberculosis is susceptible, with typical MICs ≤1 mg/L for sensitive and multidrug- resistant strains.
All enterobacteria, Pseudomonas spp. and other non-fermentative aerobic Gram-negative bacilli, including Acinetobacter spp., are resistant. Moraxella catarrhalis, Legionella spp.,Mycoplasma spp. and Chlamydia spp. are inhibited by 4–8 mg/L. Activity against Haemophilus influenzae is modest.
Among anaerobes, Clostridium perfringens and Peptostreptococcus spp. are inhibited by <2 mg/L. Typical MICs (mg/L) for Gram-negative anaerobes include: Bacteroides spp., 4–8; Prevotella spp., 1–4; Fusobacterium spp., 0.125–1.
Activity is bacteristatic against most susceptible species, but modest bactericidal activity has been demonstrated against some strains of Str. pneumoniae, C. perfringens and Bacteroides fragilis. Inhibition of toxin production by staphylococci and streptococci in the presence of sub-MIC concentrations has been described.
Linezolid may antagonize the bactericidal action of some antibiotics (e.g. gentamicin). No evidence of synergy has been found in various experimental systems with gentamicin against vancomycin-resistant Enterococcus spp. or with vancomycin, gentamicin, ciprofloxacin, fusidic acid or rifampicin (rifampin) against methicillin-resistant Staph. aureus.

獲得抵抗性

Isolates of Staph. aureus and E. faecalis for which the MIC of linezolid is raised have been obtained following serial exposure to gradients of the drug. However, induction of resistance requires many passages over several weeks. Resistance in these laboratory mutants is associated with modifications of the 23S rRNA gene.
Overall, resistance rates in clinical isolates are very low at <0.5%. Resistance is reported primarily in coagulase-negative staphylococci (1.77%) and enterococci (1.13%; mostly E. faecium), with exceptionally low resistance rates in Staph. aureus (0.06%). Risk factors for emergence of resistance include prolonged use of the drug, the presence of irremovable indwelling devices, sequestered sites of infection and low-dose therapy for infections caused by vancomycin-resistant enterococci or methicillin-resistant Staph. aureus. Resistance in clinical isolates is most often associated with gene mutations in which guanosine is replaced by uracil in the 23S rRNA. Nosocomial clonal spread of such mutants has been described in coagulase-negative staphylococci and enterococci. Resistance conferred by a novel mobile element, cfr, has been described in two isolates of staphylococci.

一般的な説明

Linezolid (Zyvox) is an oxazolidinedione-type antibacterialagent that inhibits bacterial protein synthesis. It acts in theearly translation stage, preventing the formation of a functionalinitiation complex. Linezolid binds to the 30S and 70Sribosomal subunits and prevents initiation complexes involvingthese subunits. Collective data suggest that the oxazolidindionespartition their ribosomal interaction between thetwo subunits. Formation of the early tRNAfMet-mRNA-70Sor 30S is prevented. Linezolid is a newer synthetic agent, andhence, cross-resistance between the antibacterial agent andother inhibitors of bacterial protein synthesis has notbeen seen.
Linezolid possesses a wide spectrum of activity againstGram-positive organisms, including MRSA, penicillin-resistantpneumococci, and vancomycin-resistant Enterococcusfaecalis and E. faecium. Anaerobes such as Clostridium,Peptostreptococcus, and Prevotella spp. are sensitive tolinezolid.Linezolid is a bacteriostatic agent against most susceptibleorganisms but displays bactericidal activity against somestrains of pneumococci, B. fragilis, and Clostridiumperfringens.The indications for linezolid are for complicated anduncomplicated skin and soft-tissue infections, communityandhospital-acquired pneumonia, and drug-resistant Grampositiveinfections.

応用例(製薬)

A synthetic oxazolidinone available for oral or intravenous administration. Soluble in water at a pH range of 5–9. Aqueous solutions (2 g/L) are stable at 25°C, 4°C and ?20°C for at least 3 months.

生物活性

Oxazolidinone antibiotic. Inhibits bacterial protein synthesis prior to chain initiation. Displays potent antibacterial activity against a variety of multidrug-resistant gram-positive microbes in vitro and in vivo .

薬物動態学

Oral absorption: >95%
Cmax 400 mg oral: 11–12 mg/L after 1–2 h
600 mg oral :18–21 mg/L after 1–2 h
600 mg intravenous: >15 mg/L after 1 h
Plasma half-life: c. 5.5 h
Volume of distribution :45–50 L
Plasma protein binding: 31%
absorption
Bioavailability after oral administration is almost complete. Plasma trough concentrations following oral doses of 400 mg and 600 mg every 12 h are >3.0 and >4.0 mg/L, respectively. With the higher dose, administered orally or intravenously, plasma concentrations remain above the MIC for most susceptible species throughout a 12 h dosage interval. After administration with high fat content food the maximum serum concentration achieved is lower and the peak delayed, but the area under the concentration–time curve (AUC) is unaltered.
Distribution
Linezolid is distributed widely in tissues and fluids. In human volunteers, maximum concentrations in inflammatory blister fluid averaged over 16 mg/L, with a mean penetrance of 104%. In patients undergoing hip arthroplasty, linezolid rapidly penetrates into bone, fat and muscle, achieving levels in excess of the MICs for susceptible organisms, with therapeutic concentrations maintained in the perioperative site hematoma fluid for more than 16 h. Mean penetration of linezolid into inflamed diabetic foot infection tissue is 101%, producing a concentration of 9.6 μg/g. Studies with human volunteers have also indicated good concentrations in pulmonary alveolar fluid with a mean fluid to plasma ratio of 3.2:1. When the meninges are not inflamed, the concentration in cerebrospinal fluid (CSF) is lower than that of plasma, with a CSF:plasma ratio of approximately 0.7:1. The concentration in sweat is about half that of plasma.
Other sites at which local concentrations exceed corresponding plasma concentrations, based on animal studies, include kidney, adrenal, liver and gastrointestinal tract. In a rat model of endocarditis, heart valve tissue and plasma concentrations were approximately equivalent.
Pharmacokinetic properties are unaltered in elderly patients and dose adjustment is unnecessary. Single-dose pharmacokinetic studies indicate that plasma clearance and volume of distribution are greater in children than in adults, while peak and trough serum concentrations are lower. Shorter dosing intervals (every 8 h) are therefore recommended for most therapeutic indications in children.
Metabolism
Linezolid undergoes non-renal as well as renal metabolism. Non-renal metabolism is by slow chemical oxidation in a process that does not discernibly interact with the hepatic cytochrome P450 system. The oxidants contributing to metabolism of the drug have not yet been fully elucidated, but in-vivo studies suggest the process is mediated by reactive oxygen species produced throughout the body. The metabolites produced following non-renal metabolism are an aminoethoxyacetic acid and a hydroxyethylglycine metabolite, neither of which has any significant antimicrobial activity. Non-renal clearance rates are 120 mL/min and account for almost 65% of total body clearance. Since it does not appear to act as an inducer or inhibitor of cytochrome P450 enzymes, interactions with drugs metabolized by these enzymes are unlikely to occur.
excretion
Renal clearance accounts for approximately 50 mL/min of the total body clearance of 170 mL/min. Under steady-state conditions, approximately 30% of the dose is excreted unchanged in the urine.
In populations with varying degrees of renal function (creatinine clearance range of 10–>80 mL/min) there is no evidence of alteration in total body clearance, and adjustment of dose in patients with renal insufficiency is not recommended. However, accumulation of metabolites, up to 10-fold, occurs in patients with severe renal impairment (creatinine clearance <30 mL/min). The clinical significance of this is unknown, but linezolid should be used with caution in patients with severe renal impairment. Approximately one-third of the dose is removed by hemodialysis and since total apparent clearance is increased during dialysis, one of the 12-hourly doses should be administered after the procedure. Accumulation of metabolites also occurs in patients on dialysis, with unknown clinical significance, and caution in use in hemodialysis is advised. There are no available data on pharmacokinetics in patients undergoing peritoneal dialysis or hemofiltration.
In patients with mild to moderate hepatic impairment there is no significant change to the pharmacokinetic profile. Accordingly, dosage adjustment is not recommended in patients with mild to moderate liver disease. The pharmacokinetics of linezolid in severe hepatic failure have not been studied, but as its metabolism is predominantly non-enzymatic, the pharmacokinetics would not be expected to alter significantly.

臨床応用

Linezolid is primarily used for the treatment of infections caused, or likely to be caused, by methicillin-resistant Staph. aureus, vancomycin-resistant enterococci and penicillin resistant Str. pneumoniae. Combination therapy with an antimicrobial active against Gram-negative bacteria is indicated if concomitant infection with a Gram-negative pathogen is suspected or confirmed.
Outside of licensed indications, it has been used in the treatment of bone and joint infections, endocarditis, central nervous system infections, infections in neutropenic patients and drug-resistant tuberculosis.

副作用

Most reported adverse events are mild or moderate, with reactions severe enough to lead to withdrawal of therapy occurring in less than 3% of patients.The most frequent side effects are gastrointestinal disturbances (diarrhea, nausea, vomiting and taste alteration) and headache. The reported incidence of Clostridium difficile complications is 0.2%.
Mild and transient abnormalities of liver function tests (elevation of transaminases and/or alkaline phosphatase) occur in more than 1% of patients. Skin reactions, including rashes, dermatitis, pruritus and diaphoresis, are uncommon.
Serious but infrequent adverse drug effects include myelosuppression, peripheral neuropathy, optic neuropathy and lactic acidosis. These adverse events, which probably result from inhibition of mitochondrial protein synthesis, occur primarily in patients treated for >28 days. Myelosuppression generally occurs only after more than 2 weeks of treatment and increases with longer durations. It occurs more frequently in patients with severe renal insufficiency and is reversible on discontinuation of therapy.
Reversal of cytopenias by concomitant administration of vitamin B6 has been described. Weekly monitoring of full blood count is recommended for all patients, with more frequent monitoring of those in the following categories: pre-existing anemia or thrombocytopenia; receiving concomitant drugs that may cause anemia or thrombocytopenia; severe renal insufficiency; treatment for more than 10–14 days.
Peripheral and optic neuropathy are serious but infrequent. Most cases are associated with treatment for more than 28 days (median 5 months), but neuropathies have occurred with shorter courses. In most cases optic neuropathy improved or resolved on cessation of therapy but peripheral neuropathy did not.
Lactic acidosis can occur within a week of commencing therapy but is most often seen in patients receiving prolonged treatment (median 6 weeks).
Linezolid is a weak, reversible monoamine oxidase inhibitor (MAOI) with potential interaction with adrenergic and serotonergic drugs. Co-administration of sympathomimetics, vasopressors or dopaminergic agents may lead to an enhanced pressor response. It should be co-administered with these drugs only under conditions where close observation and monitoring of blood pressure is available, and their initial doses should be reduced and then titrated to achieve the desired pressor effect. Similarly, concomitant administration of linezolid with agents that increase central nervous system serotonin concentrations can lead to serotonin toxicity (serotonin syndrome). This most commonly follows concurrent administration of selective serotonin receptor inhibitors, but can occur with tricyclic antidepressants or any MAOI. Since MAOIs and their active metabolites have long elimination half-lives, linezolid is contraindicated in patients who are taking these drugs or have taken them in the previous 2 weeks.

リネゾリド 上流と下流の製品情報

原材料

準備製品


リネゾリド 生産企業

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165800-03-3(リネゾリド)キーワード:


  • 165800-03-3
  • Linezolid (PNU-100766)
  • Linezolid API
  • Ray Nizzoli
  • Linezolid (S)-N-[[3-(3-Fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methyl]acetamide
  • Linezolid (200 mg)
  • N-({(5S)-3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide
  • Linezolid and InterMediate
  • N-{[(5S)-3-[3-fluoro-4-(Morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]Methyl}acetaMide
  • (S)-N-((3-(3-fluoro-4-Morpholinophenyl)-2-oxooxazolidin-5-yl)Methyl)acetaMide
  • Linezolid≥ 99% (Assay)
  • LINEZOLID
  • LINEZOLIDE
  • ACETAMIDE, N-[[(5S)-3-[3-FLUORO-4-(4-MORPHOLINYL)PHENYL]-2-OXO-5-OXAZOLIDINYL]METHYL]-
  • (s)-n-[[3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methyl]acetamide
  • Acetamide, N-[[(5S)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- (9CI)
  • Acetamide, N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-, (S)-
  • PNU 100766
  • U 100766
  • Zyvox
  • Linospan
  • Linox
  • N-[[(5S)-3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]- acetamide
  • Zyvoxid
  • Linezolid-13C-d3
  • N-[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxooxazolidin-5(S)-ylmethyl]acetamide (Zyvox)
  • Linezolid (Form II)
  • (S)-N-[[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl]acetamide
  • リネゾリド
  • リネゾリド (JAN)
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