生存和药效学评价关系五氟喹诺酮类原料药粒细胞减少性肺炎球菌肺感染的小鼠模型。

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恩斯特EJ, Klepser我作品CR, Doern全球之声

生存和药效学评价关系五氟喹诺酮类原料药粒细胞减少性肺炎球菌肺感染的小鼠模型。

药物治疗。2002年4月,22 (4):463 - 70。

PubMed ID

11939681 (在PubMed

]

文摘

研究目的:比较的antistreptococcal活动五氟喹诺酮类抗生素,使用粒细胞减少性肺炎球菌肺感染的小鼠模型。设计:动物实验。背景:大学附属研究中心。必威国际app动物:粒细胞减少性和控制小鼠称重24-29 g。干预:诱导的中性粒细胞减少后,肾功能衰竭,感染肺炎链球菌,老鼠收到5个氟喹诺酮类原料药/天两次72小时在感染后12小时开始。剂量选择近似0.1 x AUC0-24(从0-24小时)曲线下的面积和AUC0-24实现人类。控制老鼠收到生理盐水。生存是定期评估长达10天。至少10老鼠包含在每个队列(范围10-34)。测量及主要结果:环丙沙星、clinafloxacin grepafloxacin,左氧氟沙星,和莫西沙星在开始学习和治疗剂量对三种quinolone-susceptible隔离的肺炎链球菌缺乏突变在帕洛阿尔托研究中心,削减和gyrA。 Pharmacokinetic profile of each agent and dosing regimen was determined. A composite survival curve for all fluoroquinolones and isolates was constructed. Relationships between survival rate at 72 hours and AUC:MIC (minimum inhibitory concentration), peak:MIC, time above the MIC (percentage of dosing interval) for total and free drug concentrations were fit by using a sigmoid maximal effect (Emax) model. Survival was significantly better in the higher dosage group than in the lower dosage group. Time above MIC did not display a correlation with outcome. The AUC:MIC showed a greater correlation with outcome (R2 = 0.56 total, 0.54 free) than did peak:MIC (R2 = 0.52 total, 0.51 free). With use of composite data, total AUC:MIC ratios associated with 50%, 90%, and 99% of Emax were 34:1, 56:1, and 95:1, respectively CONCLUSIONS: In this model, efficacy was achieved with the fluoroquinolone antibiotics at dosages yielding AUC0-24 comparable to those obtained in humans. One pharmacodynamic parameter (i.e., AUC:MIC) may be applied to various fluoroquinolones and isolates of S. pneumoniae. The AUC:MIC was more predictive of outcome than was time above the MIC or peak:MIC.

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药物靶点

药物	目标	类	生物	药理作用	行动
Grepafloxacin	DNA拓扑异构酶4单元	蛋白质	流感嗜血杆菌(写明ATCC 51907株/ DSM 11121 / KW20 / Rd)	是的	抑制剂	细节