Division of Pharmacology and Chemotherapy, Department of Internal Medicine, 56126 Pisa, Italy.
Clin Pharmacokinet. 2010 Jul;49(7):439-47. doi: 10.2165/11319960-000000000-00000.
Linezolid is the first oxazolidinone agent introduced into clinical practice for use against Gram-positive bacteria that are resistant to beta-lactams and glycopeptides, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). An optimal antibacterial effect is achieved when plasma drug concentrations are above the minimum inhibitory concentration (MIC) [T>MIC] for the entire length of treatment and the ratio between the area under the plasma concentration-time curve (AUC) and the MIC (AUC/MIC) is greater than 100, as is most commonly obtained with administration of the standard dosage of linezolid 600 mg twice daily. A wide tissue distribution, including the CNS and respiratory tract, nearly linear pharmacokinetics and good tolerability are additional characteristics of linezolid. However, variability in the drug pharmacokinetics associated with clinical conditions (e.g. sepsis, burn injuries, end-stage renal disease, cystic fibrosis), haemodialysis and/or young age may lower the T>MIC and the AUC/MIC ratio, thus impairing both antibacterial activity and prevention of mutants. In most cases, changes in the dosage or in the schedule of administration (e.g. an additional [third] daily dose) may improve the effectiveness of linezolid. It is worth noting that linezolid could affect its own metabolism as a result of protein synthesis inhibition in mitochondria, and this could lead to high plasma concentrations and an increased risk of non-negligible toxicities. The latter may be reported during long-term administration of linezolid or in the presence of some pathological conditions (e.g. renal disease or kidney transplantation) associated with high plasma drug concentrations. Therefore, treatment optimization should be considered a requirement for more effective and tolerable use of the drug, particularly in special populations.
利奈唑胺是第一种用于治疗对β-内酰胺类和糖肽类药物（包括耐甲氧西林金黄色葡萄球菌（MRSA）和万古霉素耐药肠球菌（VRE））耐药的革兰阳性菌的噁唑烷酮类药物，在整个治疗过程中，当血浆药物浓度高于最低抑菌浓度（MIC）[T>MIC]，且血浆浓度-时间曲线下面积（AUC）与 MIC 的比值（AUC/MIC）大于 100 时，可获得最佳的抗菌效果，这通常是通过给予利奈唑胺标准剂量 600mg，每日两次获得的。利奈唑胺还具有广泛的组织分布（包括中枢神经系统和呼吸道）、接近线性的药代动力学特征和良好的耐受性等特点。然而，与临床状况（如败血症、烧伤、终末期肾病、囊性纤维化）、血液透析和/或年龄相关的药物药代动力学的变异性可能会降低 T>MIC 和 AUC/MIC 比值，从而削弱抗菌活性和防止突变体的产生。在大多数情况下，改变剂量或给药方案（例如，增加每日第三剂）可能会提高利奈唑胺的疗效。值得注意的是，利奈唑胺可能会因抑制线粒体蛋白质合成而影响自身的代谢，这可能导致血浆浓度升高，并增加不可忽视的毒性风险。后者可能在长期使用利奈唑胺或在存在与高血浆药物浓度相关的某些病理状况（如肾病或肾移植）时报告。因此，治疗优化应被视为更有效和耐受药物使用的要求，特别是在特殊人群中。
