Pharmacokinetics Of Linezolid In Rat Plasma, Brain Tissue And Cerebrospinal Fluid

Part1Determination of linezolid in rat plasma、brain tissues and cerebrospinal fluid byHPLCAbstract Objective：To establish a method research and clinical drug concentrationmonitoring. Methods： Separation was carried out on a Inertsil ODS-SP column（4.6×250mm，5μm） after the protein in plasma、brain tissue and CSF were deposited withmethanol, the mobile phase consisted of acetonitrile-water （25:75,V：V）,the flow rate was1ml.min^-1. The detection wavelength was254nm and the column temperature was30℃.Results: In plasma the scope of linezolid standard curve were0.5～50μg·ml^-1with a goodlinear correlation（r=0.9995）.The minimum concentration of linezolid was0.2μg·ml^-1. Thedaytime RSD of plasma specimen concentration of linezolid was≤1.5%and interday RSDof plasma specimen was≤3%. The recovery rates in the treating group were98%～101%.Inbrain tissue the scope of linezolid standard curve were0.5～50μg·ml^-1with a good linearcorrelation（r=0.9991）.The minimum concentration of linezolid was0.2μg·ml^-1. The daytime RSD of plasmaspecimen was≤6%and interday RSD of plasma specimen was≤2.5%. The recovery rates in the treating group were97%～104%.In CSF the scope of linezolid standard curve were1～50μg·ml^-1with a good linear correlation（r=0.9991）.The minimum concentration of linezolid was0.5μg·ml^-1. The daytime RSD ofplasma specimen was≤6%and interday RSD of plasma specimen was≤3%, The recoveryrates in the treating group were97%～101%. There were non-interference endogenousmaterial for detection linezolid concentration in plasma、brain tissue and CSF. Conclusions:The methods of detemining the concentration of linezolid in rat plasma、brain tissues and CSFby HPLC for pharmacokinetics is simple、rapid and accurate. Part2pharmacokinetics of Linezolid in rat plasma, brain tissue and cerebrospinal fluidObjective: To explore pharmacokinetics of linezolid in rat plasma、brain tissueand cerebrospinal fluid so as to provide evidence for the clinical treatment of central nervessystem infection.Methods: A total of78SD rats plasma、brain tissue and cerebrospinal fluidsamples were collected and pharmacokinetic parameters of linezolid were estimated after asingle dose of linezolid injection. Results: The maximum concentrations (C_max) of linezolidin rat plasma、brain tissue and cerebrospinal fluid were31.39μg/ml、5.11μg/ml and23.97μg/ml, the elimination half life time(t_1/2) were2.67h、2.42h and1.99h. The total areasunder the Concentration-time curve(AUC_{0～∞})of linezolid in rat plasma、brain tissue andcerebrospinal fluid were134.55μg.h.ml^-1、28.23μg.h.ml^-1and136.43μg.h.ml^-1. Thepenetration rate of linezolid in CSF was76.36%. Conclusion: Linezolid could rapidly attainan optimal trough concentration in cerebrospinal fluid. It has a good pharmacokineticscharacter and permeability.