抗结核药物及方案对结核性脑炎治疗作用及药物的药代动力学/药效学研究

目的 测定三种抗结核药在健康和结核性脑膜炎小鼠脑组织中的浓度,评价几种单药和联合方案抗肺结核和结核性脑膜炎的活性;评价其药代动力学/药效学(PK/PD)参数.方法 通过小鼠静脉感染H37Rv 建立结核性脑膜炎模型,健康和结核性脑膜炎小鼠分别连续给予利福平(RFP)、左氧氟沙星(Lfx)、莫西沙星(Mfx)5 d 后,于...

Study on therapeutic effect of anti-TB drugs and regimens for tuberculosis meningitis and PK /PD of these drugs

Objective To determinte the concentrations of three anti-TB drugs are increased in the brain tissue of health and TB meningitis（MTB） model mice,study the pharmacokinetics/pharmacodynamics （PK/PD） parameters of them in plasma and brain tissue using healthy and MTB model mice,evaluate the activities of these drugs respectively and combinations of them,provide information for the treatment of MTB based on their activities and parameters.Methods MTB mice model was developed through injecting H37Rv into the tail vein of mice.After administrated RFP,Lfx,Mfx for 5 days,the plasma and brain tissue of healthy and MTB mice were gotten at different time points and the concentrations of these drugs were determined by HPLC,and then obtain the PK and PK/PD parameters.The mice were given Lfx,Mfx and other drugs usually used to therapy TB alone or combination,CFU in lungs and brain tissues were obtained after treatment for 8 weeks and these data together with the PK and PK/PD parameters were analyzed to evaluate the efficiency of treating pulmonary TB and MTB.Results The AUC0-24 of RFP,Lfx,Mfx were increased by 56.0%,148.5%,80.4%,AUC0-24/MIC were 445.0,16.5,7.4 respectively;after treatment for 8 weeks,except PZA,Lfx that the CFU were decreased more.For MTB,every groups except Lfx were effective and INH,RHPto,RHLfx,RHMfx were more effective.Conclusions The amounts of drugs entering into the brain tissue increase while the brain was infected by H37Rv when compared with that of healthy mice;RHPto,RHLfx,RHMfx are effective combinations to therapy MTB,so all of them can be choosed as therapeutic remedy for different patients.