莫昔沙星的治疗优势也显示在一些动物模型中。Bayer AG药物研究中心的Dalhoff A使用小鼠呼吸道感染模型研究了莫昔沙星对肺炎链球菌和肺炎衣原体的活性,小鼠经鼻腔感染后,用本品口服治疗,50 mg/kg剂量可降低肺炎链球菌的细菌计数为原来的1%。小鼠感染肺炎衣原体后用本品10 mg/kg治疗,显示肺中病原体根除或在肺组织中显著地降低了菌丛的形成。 关于动物的药代动力学研究,Bayer AG药物研究中心的Siefert H M等的试验结果证实了大鼠的药代动力学是有性别依赖性的。雌性与雄性大鼠比较,iv后,t1/2=1.4对1.2 h或分布容积Vss为4.2对4.01 L/kg,无差异。相反,血浆的总消除率雌性(4.8 L/(kg*h))明显比雄性(2.8 L/(kg*h)/L)高。口服给药后,雌性大鼠的Cmax(0.72对2.9 ml/L)较低,AUC(0.47对2.8(kg*h)/L)要小,生物利用度(25%对78%)也较差。通过人的药代动力学研究,Stass HH等认为,人服用本品后吸收良好,消除半衰期约为12 h,分布容积3~4L/kg,药物耐受性较好,单剂量服用200mg时,药动学无性别和年龄的差异。 莫昔沙星是由德国Leverkusen和Wuppertal的Bay AG研究实验室开发的。现正在世界各国进行多中心临床试验,1997年申请在中国作临床研究,1998年初已获批准。 氟喹诺酮类抗菌药的开发研究在不断深入,伴随而来的细菌耐药性的迅速发展与交互传播越来越引起人们的重视,如何加强细菌耐药性监测,制订合理用药的策略和指导原则,避免应用对病原菌作用较弱的品种以及限制用于农、畜牧业等,预计将成为今后重点研究的新课题。
作者单位:(国家药品监督管理局药品审评中心,北京 100050)
参考文献
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