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目的建立高效液相色谱法(HPLC)检测微透析样本中左旋奥硝唑方法,并应用该方法进行左旋奥硝唑大鼠灌胃给药后脑内药动学研究,为该药的临床研究提供数据支持。方法在活体大鼠脑内置入探针,利用脑微透析在线取样技术,连续收集第三脑室透析液,并用HPLC进行左旋奥硝唑浓度测定。应用DAS2.0软件拟合药动学参数。结果左旋奥硝唑可迅速透过血脑屏障,脑内未发生消旋体转化,50、100、200 mg.kg-1 3个剂量组的主要药动学参数:ρmax分别为(0.999±0.28)、(2.624±1.493)、(6.207±3.84)mg.L-1;tmax分别为(1.333±0.289)、(1.375±0.25)、(1.5±0)h;t1/2分别为(5.972±2.594),(1.594±0.264)、(1.115±0.564)h;AUC0-t分别为(2.304±0.132)、(5.068±1.388)、(8.898±3.333)mg.h.L-1。结论本实验评价了左旋奥硝唑血脑屏障的通透性及脑内药动学行为,为单一对映体用于脑内厌氧菌感染的治疗和分析中枢神经系统的不良反应提供依据。
OBJECTIVE To establish a high performance liquid chromatography (HPLC) method for the detection of levo-ornidazole in microdialysis samples, and to study the pharmacokinetics of L-ornidazole after intragastric administration by this method. data support. Methods The probes were placed into the brain of living rats and the third ventricle dialysate was continuously collected by on-line sampling technique of brain microdialysis. The contents of levodinal ornidazole were determined by HPLC. Application of DAS2.0 software to fit pharmacokinetic parameters. Results Levodronazole could rapidly penetrate the blood-brain barrier, and no racemic transformation occurred in the brain. The main pharmacokinetic parameters of 50,100,200 mg.kg-1 dose groups were ρmax (0.999 ± 0.28 ), (2.624 ± 1.493) and (6.207 ± 3.84) mg.L-1, respectively; tmax was (1.333 ± 0.289), (1.375 ± 0.25) and (1.594 ± 0.264) and (1.115 ± 0.564) h, respectively; AUC0-t was (2.304 ± 0.132), (5.068 ± 1.388) and (8.898 ± 3.333) mg.hL-1, respectively. Conclusion This experiment evaluated the permeability and intracranial pharmacokinetics of L-ornidazole blood-brain barrier and provided the basis for single enantiomer for the treatment of anaerobic infections in the brain and the analysis of adverse reactions in the central nervous system.