Rakicidin B药动学和安全性初步研究  

Preliminary studies on pharmacokinetics and safety evaluation of rakicidin B

作　　者：江红[1] 周剑[1] 陈丽[1] 赵薇[1] 江宏磊[1] 魏宗有[1] 陈忠[1] 连云阳[1] 林风[1] Jiang Hong;Zhou Jian;Chen Li;Zhao Wei;Jiang Hong-lei;Wei Zong-you;Chen Zhong;Lian Yun-yang;Lin Feng(Fujian Key Laboratory of Screening for Novel Microbial Products,Fujian Institute of Microbiology,Fuzhou 350007)

机构地区：[1]福建省微生物研究所福建省新药(微生物)筛选重点实验室

出　　处：《中国抗生素杂志》2019年第12期1362-1365,共4页Chinese Journal of Antibiotics

基　　金：国家重点研发计划(No.2018YFC0311004);国家“十三五”重大新药创制项目(No.2019ZX09721001-002-005);福建省省属公益类科研院所基本科研专项(No.2019R11020006-6)

摘　　要：目的对海洋微生物来源的化合物rakicidin B开展药动学和安全性初步评价。方法采用静脉和口服给药初步研究rakicidin B的药动学和急性毒性。鼠伤寒沙门菌回复突变试验检测rakicidin B的遗传毒性。结果 SD大鼠口服给予5.0mg/kg rakicidin B后血浆中基本检测不到药物;SD大鼠静脉0.2mg/kg,Cmax为490.67ng/mL,AUC(0~0.083)为376.07h·ng/mL;rakicidin B口服毒性低,大鼠口服最大耐受量MTD大于1000mg/kg;静脉毒性MTD大于1.0mg/kg;rakicidin B在本试验所确定的125μg/皿剂量范围内,对鼠伤寒沙门菌回复突变(Ames)标准试验菌株无明显致突变性。结论 Rakicidin B总体安全性好,无急性毒性作用及无遗传毒性。研究结果为rakicidin B进一步的临床前试验研究提供参考。Objective To evaluate the pharmacokinetics and safety of rakicidin B.Methods The pharmacokinetics and acute toxicity of rakicidin B were studied by intravenous and oral administration.Ames test was performed to investigate the genotoxicity of rakicidin B.Results Rakicidin B showed low oral toxicity,oral toxicity MTD>1000 mg/kg,venous toxicity MTD>1.0 mg/kg.After the oral administration of 5.0 mg/kg rakicidin B to rats,the drug was not detected in plasma.After the intravenous injection of 0.2 mg/kg rakicidin B,Cmax in the blood was 490.67 ng/mL,and AUC(0~0.083)was 376.07 h·ng/mL.Rakicidin B with 125μg/dish final concentration was not genotoxic based on the Ames Test bacterial aberration.Conclusion Rakicidin B exhibited good safety,no acute toxicity,and no genotoxicity.The results of the studies can provide references and important guiding significance for the clinical trial of rakicidin B.

关 键 词：Rakicidin B 药动学 毒理学 安全性评价 

分 类 号：R9[医药卫生—药学]