Vardakas K Z, Kioumis I, Falagas M E
Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece.
Curr Drug Metab. 2009 Jan;10(1):2-12. doi: 10.2174/138920009787048446.
Linezolid is the first antibiotic of a new class (oxazolidinones). It inhibits protein synthesis by binding to the bacterial 23S ribosomal RNA of the 50S subunit, thus blocking the formation of the functional 70S initiation complex, but it does not inhibit peptidyl transferase. Therefore, its mechanism of action is unique and cross resistance is unlikely to occur; however, resistant strains have already been reported, but the rate of resistance is low in surveillance programs. Linezolid has a favorable pharmacokinetic profile. It is rapidly absorbed when administered orally, and it is 100% bioavailable, thus allowing early switch from intravenous to oral administration. The maximum plasma concentration (range between 13.1+/-1.8 to 19.5+/-4.5 microg/ml according to the route of administration, studied population and dosages administered to subjects) is achieved 1-2 hours after the first dosage. It penetrates readily to most tissues of the human body at concentrations much higher than that of the minimal inhibitory concentrations of the targeted pathogens. It is metabolized by oxidation in two major inactive metabolites and is eliminated mainly through the kidneys. Linezolid is bacteriostatic for staphylococci and enterococci but bactericidal for pneumococci and kills bacteria in a time-dependent fashion. It has been studied in several randomized controlled trials and has been approved for the treatment of patients with Gram positive bacterial infections (community-acquired and nosocomial pneumonia, skin and soft tissue infections, and infections due to vancomycin-resistant enterococci) including these due to multidrug-resistant strains. Careful and judicious use is warranted to preserve the activity of this important antibiotic.
利奈唑胺是新型（恶唑烷酮类）的首个抗生素。它通过与50S亚基的细菌23S核糖体RNA结合来抑制蛋白质合成，从而阻断功能性70S起始复合物的形成，但它不抑制肽基转移酶。因此，其作用机制独特，不太可能出现交叉耐药性；然而，已有耐药菌株的报道，但在监测项目中耐药率较低。利奈唑胺具有良好的药代动力学特征。口服给药时吸收迅速，生物利用度为100%，因此可以早期从静脉给药转为口服给药。首次给药后1 - 2小时达到最大血浆浓度（根据给药途径、研究人群和受试者给药剂量，范围在13.1±1.8至19.5±4.5微克/毫升之间）。它能以远高于目标病原体最低抑菌浓度的浓度轻易渗透到人体的大多数组织中。它通过氧化代谢为两种主要的无活性代谢产物，主要通过肾脏排泄。利奈唑胺对葡萄球菌和肠球菌具有抑菌作用，但对肺炎球菌具有杀菌作用，并以时间依赖性方式杀灭细菌。它已在多项随机对照试验中进行了研究，并已被批准用于治疗革兰氏阳性细菌感染患者（社区获得性和医院获得性肺炎、皮肤和软组织感染以及耐万古霉素肠球菌引起的感染），包括由多重耐药菌株引起的感染。必须谨慎明智地使用以保持这种重要抗生素的活性。
