噁唑烷酮类抗菌药骨髓抑制毒性的大鼠实验预测模型  

Rat model of predicting myelosuppression potential of oxazolidinone antimicrobial agents

作　　者：王海林[1,2] 黄艳琴 刘世聪 许云华 王雯 袁征宇 朱焕章[1] 

机构地区：[1]复旦大学生命科学学院,上海200433 [2]盟科医药技术(上海)有限公司,上海201203

出　　处：《中国抗生素杂志》2014年第12期881-884,910,共5页Chinese Journal of Antibiotics

摘　　要：目的建立一个时间短且有效的大鼠骨髓抑制毒性实验模型,以缩短噁唑烷酮类抗菌药骨髓抑制毒性评价周期、减少化合物的用量、降低新型噁唑烷酮类抗菌药的开发成本。方法通过研究噁唑烷酮类抗菌药利奈唑胺和在研MRX-I对大鼠用药1和2周后的骨髓抑制毒性,比较其骨髓抑制毒性敏感指标网织红细胞以及血小板数值与实验周期的关系,并与文献及临床数据进行比对。结果利奈唑胺给药组和MRX-I给药组其大鼠1周和2周的网织红细胞以及血小板数据以及剂量趋势高度一致;且数据显示MRX-I比较利奈唑胺更安全。利奈唑胺和MRX-I的实验结果也与文献报道及临床数据一致。结论可以通过1周大鼠毒性实验模型进行预测噁唑烷酮类抗菌药2周左右、甚至更长期的潜在骨髓抑制毒性趋势,为该类抗菌药骨髓抑制毒性的快速筛选提供了依据。Objective Develop a rapid and effective rat model for prediction of oxazolidinone-induced myelosuppression, in order to shorten screening period, reduce compounds consumption, and cut cost of the development of novel oxazolidinone antimicrobial agents. Methods Investigate myelosuppression caused by linezolid and the investigational drug MRX-I in rat for 1 week and 2 weeks, to compare the reticulocyte and platelet counts as the sensitive indexes of myelosuppression, as well as data in literature including clinical outcome. Results The reticulocyte and platelet counts changes are highly consistent in rat after dosing 1 week and after dosing 2 weeks of linezolid and MRX-I, which also suggests MRX-I are safer than Linezolid. These data are also consistent with the data in literature and clinical outcome. Conclusion Short-term （1 week） rat toxicity model can predict the potential myelosuppression trend after dosing oxazolidinone antimicrobial for ca. 2 weeks or even longer, which pave the way for a rapid screening of myelosuppression of this class.

关 键 词：MRX-I 利奈唑胺 噁唑烷酮 大鼠 网织红细胞 血小板 骨髓抑制毒性 

分 类 号：R978[医药卫生—药品]