中药狼毒大戟表观体内残留量动力学  

Apparent Pharmacokinetics of the Residual Dose of Euphorbia fischeriana Steud

作　　者：何华红[1] 谢智达[2] 李薇[1] 何永平[1] 严小红[1] 江英桥[1] 

机构地区：[1]广州市药品检验所,510160 [2]广东药学院,广东广州510006

出　　处：《时珍国医国药》2011年第6期1319-1320,共2页Lishizhen Medicine and Materia Medica Research

基　　金：国家科技支撑计划药品安全关键技术研究资助课题(No.2006BAI14B01)

摘　　要：目的测定小鼠腹腔注射（ip）狼毒大戟乙醇提物表观体内残留量动力学参数,为临床合理用药提供依据。方法采用B liss法评定狼毒大戟醇提物的急性毒性,求出其腹腔注射和灌胃（ig）两种给药途径的LD50值,根据ip的＂对数剂量-死亡机率单位＂直线（D-P直线）求出其LD90值,取小鼠120只,按性别、体重组间一致原则分为6组,每组20只,雌雄各半,ip药物,剂量为1/2 LD90,体积为0.5 m l/只,每组小鼠给药2次,按1,2,4,8,24,48 h顺序设置各组给药间隔,连续观察7 d,根据每组小鼠累积死亡数计算狼毒大戟表观体内残留量药动学参数。结果狼毒大戟醇提物ip给药LD50为130.39 mg·kg-1（95%的可信限为118.9~144.62 mg·kg-1）;体内代谢过程属二房室模型;主要表观药动学参数如下：α为0.315 h-1,β为0.01 h-1,K21为0.057 h-1,K10为0.055 h-1,K12为0.212 h-1,T1/2（α）为2.2 h,T1/2（β）为69.5 h,T1/2（K21）为12.06 h,T1/2（K10）为12.7 h,T1/2（K12）为3.26 h;狼毒大戟醇提物ig给药LD50为3.53 g·kg-1（95%的可信限为3.19~3.91 g·kg-1）;F值（ipLD50/igLD50）约为：0.04。结论该方法适合狼毒大戟体内残留量药代动力学评价;狼毒大戟醇提物体内代谢半衰期很长,可能在体内重要器官有蓄积,用药时要考虑其在体内的蓄积毒性,测定结果为临床合理用药提供了依据。Objective To determine the apparent residual dose kinetic parameters of Euphorbia fischeriana Steud in mice for rational use of the drug.Methods Acute toxicity of Euphorbia fischeriana steud was evaluated by Bliss method.120 were divided into 6 groups（n = 20） based on the same principles of gender and body weight.Every mouse was administered twice by ip.The doses were 1/2LD90 and the time interval of administration was 1,2,4,8,24 and 48 h,respectively.After continuous observation for 7 days,apparent pharmacokinetics parameters of the residual dose were calculated according to the mortality of mice.Results LD50 of ip Euphorbia fischeriana Steud ethanol extract was 130.39 mg·kg-1（95% confidence limit 118.9~144.62 mg·kg-1）.Pharmacokinetics of Euphorbia fischeriana Steud could be described by the two-compartment open model.The main apparent pharmacokinetic parameters were as follows： α=0.315 h-1,β=0.01 h-1,K21=0.057 h-1,K10=0.055 h-1,K12=0.212 h-1,T1/2（α）=2.2 h,T1/2（β）=69.5 h,T1/2（K21）=12.06 h,T1/2（K10）=12.7 h,T1/2（K12）=3.26 h.LD50 of ig Euphorbia fischeriana Steud ethanol extract was 3.53 g·kg-1（95% confidence limit 3.19~3.91 g·kg-1）;the value of F（ipLD50/igLD50） was about 0.04.Conclusion The method can be used in pharmacokinetic study of Euphorbia fischeriana Steud.The ethanol extract of Euphorbia fischeriana Steud has a long half-life and may accumulate in the vital organs of body.The data are of benefit for rational use of the drug.The cumulative toxicity should be considered when it is used.

关 键 词：狼毒大戟 LD50 急性死亡率法 药代动力学 

分 类 号：R285.5[医药卫生—中药学]