Rakicidin B药动学和安全性初步研究

Preliminary studies on pharmacokinetics and safety evaluation of rakicidin B

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.