Di Rocco P H, Nacucchio M C, Sordelli D O, Mancuso F, Hooke A M
Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Infection. 1992 Nov-Dec;20(6):360-4. doi: 10.1007/BF01710685.
The therapeutic efficacy of liposomal cefoperazone against Pseudomonas aeruginosa was investigated in a granulocytopenic mouse model of acute lung infection. Granulocytopenia was induced in mice by intraperitoneal (i.p.) injection of 200 mg/kg cyclophosphamide. Mice were challenged by exposure to an aerosol containing P. aeruginosa and were treated i.p. with liposomal cefoperazone prepared by the dehydration-rehydration method. The half-life of free cefoperazone in the lungs following i.p. administration of the liposomal drug was significantly lengthened (13 min vs. 261 min), and the cefoperazone activity in the lungs remained above the MIC longer after administration of liposomal cefoperazone than after treatment with cefoperazone. Liposomal cefoperazone was more effective than cefoperazone alone in preventing death of granulocytopenic mice from lethal pulmonary challenge with P. aeruginosa (75% vs. 38% survival, p = 0.031). Finally, P. aeruginosa was cleared faster from the lungs of mice treated with liposomal cefoperazone when compared with those treated with cefoperazone. This study shows that incorporation of cefoperazone into liposomes enhances the activity of the antibiotic against P. aeruginosa in a granulocytopenic host.
在粒细胞减少的急性肺部感染小鼠模型中，研究了脂质体头孢哌酮对铜绿假单胞菌的治疗效果。通过腹腔注射200mg/kg环磷酰胺诱导小鼠粒细胞减少。小鼠通过暴露于含有铜绿假单胞菌的气溶胶中受到攻击，并用脱水-复水法制备的脂质体头孢哌酮进行腹腔治疗。腹腔注射脂质体药物后，游离头孢哌酮在肺中的半衰期显著延长（13分钟对261分钟），并且脂质体头孢哌酮给药后肺中头孢哌酮活性保持高于最低抑菌浓度的时间比头孢哌酮治疗后更长。在预防粒细胞减少的小鼠因铜绿假单胞菌致死性肺部攻击而死亡方面，脂质体头孢哌酮比单独使用头孢哌酮更有效（存活率75%对38%，p=0.031）。最后，与用头孢哌酮治疗的小鼠相比，用脂质体头孢哌酮治疗的小鼠肺中铜绿假单胞菌清除得更快。这项研究表明，将头孢哌酮包裹在脂质体中可增强抗生素在粒细胞减少宿主中对铜绿假单胞菌的活性。
