摘要
目的:研究乌苏里黎芦生物碱(Veratrum n igrum L.var.Ussurience Nakai alkaloids,VnA)在小鼠体内的药代动力学及其蓄积性毒性。方法:用小鼠急性死亡率法估测iv VnA的LD50及药代动力学参数,判定VnA的蓄积毒性。结果:测得VnA的LD50(iv)为702μg/kg,95%可信限为681.83μg/kg^724.18μg/kg。对数体存率?时间曲线呈一室模型,其消除过程遵循一级动力学。VnA的药代动力学参数为:K 0.32m in,t1/2 2.17m in,Vd 2.02μg/kg,AUC∞960.20μg/kg.m in,CL 0.65μg/kg.m in。小鼠每日140.2μg/kg(1/5 LD50),连续一个月,仍未见小鼠死亡,求得VnA的Kc>6,可见VnA无明显蓄积作用。结论:VnA静脉注射后其毒性成分在小鼠体内的动力学行为可用一室开放模型加以描述,其消除遵循一级动力学。VnA的毒性成分在体内消除极快,其半衰期仅为2.17分钟。VnA虽急性毒性很强但无明显蓄积毒性。
Aim： To investigate the pharmacokinetics and cumulative toxicity in mice of Veratrum nigrum L. var. ussuriense Nakai alkaloids （VnA）. Methods： the LD50 was determined with reference to the routine procedures. Cumulative factor （Kc）, an index used to evaluate cumulative toxicity, was measured based on the ratio of ∑LD50 （n） to LD50. The toxicological effect method was utilized to study the pharmacokinitic profile of VnA. Result： （1） LD50 is 702μg/kg with a 95% confidence limit of 681.83μg/kg～724.18μg/kg. （2） Pharmacokinetic study： The RR-time curve could be described by an one-compartment model. It was found that the drug eliminated from the body in a monoexponential manner with the pharmacokinetic parameters of tl/2 2.17 min, Vd 2.02 μg/kg, AUC 960.20μg/kg·min, Cl 0.65 μg/kg·min. （3） Cumulative toxicity： ∑LD50 （n） 〉 6LD50. Therefore, VnA can be considered to be devoid of significant cumulative toxicity. Conclusion： The pharmacokinetic behaviour of VnA complies with one-compartment model. The elimination of the drug in mice follows the first-order kinetics with an extremely short harf-life （2.17 min）. Both Kc and tl/2 indicate that VnA has no significant cumulative toxicity, despite its high acute toxicity, due to the extremely rapid elimination of the drug.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2006年第3期51-53,共3页
Pharmacology and Clinics of Chinese Materia Medica
关键词
乌苏里黎芦碱
半数致死量
药代动力学
蓄积性毒性
Veratrum nigrum L. var. ussuriense Nakai alkaloids
toxicological effect method
cumulative toxicity
LD50
