炎症和高渗溶液对莫西沙星透过血-脑脊液屏障影响的研究及疗效评价

Effect of Inflammation and Hypertonic Solution on the Permeability of Moxifloxacin Across the Blood-cerebrospinal Fluid Barrier and Evaluation on Therapeutic Efficacy

目的:探讨炎症以及高渗溶液对血-脑脊液屏障通透性的影响。方法:比较健康小鼠与结核性脑膜炎小鼠模型脑组织中莫西沙星的含量,以及利用自身对照的方法,测定患者不用和用甘露醇后脑脊液中莫西沙星含量的变化。结果:当炎症存在时,莫西沙星进入脑组织的含量增加,药物的药-时曲线下面积(AUC)增加了21.5%,经t检验,P<0.05,有显著性差异;药效学试验表明在单药治疗8周后,脑组织中活菌计数(cfu)降低,经t检验,P<0.05,有显著性差异,具有统计学意义;患者在口服莫西沙星2h后给予甘露醇,使得药物在脑脊液的含量增加了1～4倍。结论:在炎症和(或)高渗溶液存在情况下,药物透过血-脑脊液屏障的量将增加。

OBJECTIVE： To study the effects of inflammation and hypeitonic solution on the permeability of moxifloxaein across the blood-cerebrospinal fluid barrier. METHODS： The concentration of moxifloxaein in the brain tissue of the healthy mice was compared with that in tuberculosis meningitis model mice. The change of the concentration of moxifloxacin in the brain tissue of patients receiving mannitol or in those without receiving mannitol was determined by using self control. RESULTS： The presence of inflammation was associated with increased concentration of moxifloxacin in brain tissue and 21.5% increase of AUC （area under the curve） of moxifloxacin, showing significant differences via t-test （P 〈 0.05 ）. Pharmaeodynamic study of moxifloxaein indicated that after treatment of 8 weeks with single drug, the cfu （ colony-forming unit） in brain tissue was decreased, showing significant differences via t-test （P 〈 0.05）. Administration of mannitol 2 hours following oral administration of moxifloxacin led to 1 -4 fold increase in the concentration of moxifloxacin in eerebrospinal fluid （CSF）. CONCLUSION： The permeability of moxifloxacin across the blood-cerebrospinal fluid barrier increases at the presence of inflammation and/ or hypertonie solution.