Ma Jian-Li, Gao Lei, Li Xiang, Chu Wan-Li, Feng Yong-Qiang, Wang Xiao-Qin, Zhang Qing-Zhe
Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, 51 Fucheng Road, Beijing, 100048, China,
Eur J Drug Metab Pharmacokinet. 2015 Sep;40(3):355-61. doi: 10.1007/s13318-014-0209-6. Epub 2014 Jun 13.
Linezolid is effective on many resistant organisms for the treatment of severe infections in burns. However, its pharmacokinetics was difficult to predict after major burns. The study aimed to describe the pharmacokinetic properties of linezolid administered intravenously at a dose of 10 mg/kg in severely burned rabbits in comparison to that in non-burns. Linezolid concentrations were quantitatively analyzed by high-performance liquid chromatography. The direct consequence of the physiological changes after burn injury was lower plasma linezolid concentrations. In addition, burn injury induced significantly altered pharmacokinetic parameters with higher inter-individual variability. The distribution volume and clearance rate were increased (2.88 vs. 1.92 L/kg, P > 0.05; 0.28 vs. 0.20 L/h/kg, P < 0.05), and the AUC0-∞ was significantly lower (37.99 vs. 51.47 mg/L h, P < 0.05). However, there were almost no changes in half-life and mean residence time. These results suggested that therapeutic drug monitoring and dosage individualization of linezolid in patients with severe burns were necessary.
利奈唑胺对许多耐药菌有效，可用于治疗烧伤中的严重感染。然而，大面积烧伤后其药代动力学难以预测。本研究旨在描述与未烧伤的兔子相比，严重烧伤的兔子静脉注射10mg/kg剂量利奈唑胺后的药代动力学特性。利奈唑胺浓度通过高效液相色谱法定量分析。烧伤后生理变化的直接后果是血浆利奈唑胺浓度降低。此外，烧伤导致药代动力学参数显著改变，个体间变异性更高。分布容积和清除率增加（分别为2.88 vs. 1.92L/kg，P>0.05；0.28 vs. 0.20L/h/kg，P<0.05），AUC0-∞显著降低（37.99 vs. 51.47mg/L h，P<0.05）。然而，半衰期和平均驻留时间几乎没有变化。这些结果表明，对严重烧伤患者进行利奈唑胺的治疗药物监测和剂量个体化是必要的。
