二甲苯胺噻唑在羊、兔体内的药动—药效同步模型的研究  

Studies on the Simultaneous Pharmacokinetic-pharmacodynamic (PK-PD) modeling of Xylazole in Sheep and Rabbits

作　　者：李涛[1] 刘雅红[1] 李继昌[1] 刘秀华[1] 易洪斌 李时峰 乔桂林[1] 

机构地区：[1]东北农业大学,黑龙江哈尔滨150030

出　　处：《黑龙江畜牧兽医》2000年第12期1-6,共6页Heilongjiang Animal Science And veterinary Medicine

基　　金：国家自然科学基金项目! (C0 30 2 0 80 7) .该项目获省科技进步三等项 (960 4 50 1 )

摘　　要：以气相色谱 (GC)、高效液相色谱 (HPLC)、荧光分析与放射免疫 (RIA)等方法为检测手段 ,提供药动学数据 ;以脑电、心电、肌电等数据作药效学定量指标 ,经计算机拟合后 ,获得二甲苯胺噻唑 (XL)的药动─药效 (PK -PD)同步模型参数。血药动力学与脑电拟合同步模型参数为N(Hill系数 ) =0 .1 0 1 2 3 ,Keo(效应室消除速率常数 ) =0 .2 2 0 9min- 1 ,t1 2 keo(血药浓度 -药效平衡半衰期 ) =3 .1 4min ,Ec5 0 (半效浓度 ) =0 .30 4 μg/mL ,Emax(理论最大效应 ) =0 .2 2 1 4 (% ) ,AUE1 (E -t曲线下面积预报值 ) =0 .2 4 2 7μg/mL·min ,AUE2 (E -t曲线下面积 ) =0 .2 1 4 0 μg/mL·min .r=0 .992 6。脑药动力学与脑电拟合的同步模型参数 :N =0 .9766 ,Keo =0 .2 2 0 9min- 1 ,t12 keo=3 .1 378min ,Ec5 0 =0 .3954μg/mL ,Emax =0 .2 2 1 4 (% ) .AUE1 =0 .1 60 5μg/mL·min ,AUE2 =0 .1 835μg/mL·min ,r=0 .9937。血药动力学与肌电拟合的同步模型参数 :N =0 .1 379,Keo =0 .2 2 65min- 1 ,t12 keo=3 .0 596min ,Ec5 0 =0 .780 4 μg/mLEmax =0 .872 1 (% ) ,AUE1 =0 .5357μg/mL·min ,AUE2 =0 .5584μg/mL·min ,r=0 .9989。The simultaneous pharmacokinetic-pharmacodynamic modeling of xylazole were studied by Gas chromatography(Gc)、high-performanceliquid chromatography(HPLC)、Spectrofluometry,Radioimmunoassayelectroencephalography(EEG)and electromyography(EMG) method.The pharmacokinetic data were analyzedby GC、HPLC RIA method,and the pharmacodynamlc data were measured by ECG.EEG and EMG method.The parameters of pharmacokinetic-pharmacodynamic simultaneous modeling were estimated by cpu-pk-pdcomputer program.on the hasis of changes of Acethlcholine(Ach).Norepinephrine(NE) and β-Endorphin(β-Ep) levels after intramuscularadministration in blood.CSF.pituitary and hypothalamus,we explainecdtheir sedation analgsic and muscular relaxation effective mechanism,and their interrelation. The sampling and effect-quanlity assay were simulcast on same Animals. The parameter of simultaneous pharmacokinetic-pharmacodynamicmodeling of xylazole as follows: A.Parameters of simultaneous PK-PD modeling for blood kinetics-EEG: N(Hill coefficient)=0.10123,Keo=0.2209 min -1 ,t 12Keo =3.14 min, E c50 =0.304 μg/mL,Emax=0.2214(%),AUE 1=0.02427 μg/mL·min,AUE 2=0.2140 μg/mL·min,r=0.9926; B.Parameters of simultaneous PK-PD modeling for CSF kinetics-EEG: N=0.9766,Keo=0.2209 min -1 ,t 12Keo =3.1378 min,E C50 =0.3954 μg/mL,Emax=0.2214(%),AUE 1=0.1605 μg/mL·min, AUE 2=0.1835 μg/mL·min,r=0.9937; C.Parameters of simultaneoas PK-PD modeling for blook dinetics-EMG: N=0.1379,Keo=0.2265 min -1 ,t 12Keo =3.0596 min,E c50 =0.7804 μg/mL,Emax=0.8721(%),AUE 1=0.5357 μg/mL·min, AUE 2=0.5584 μg/mL·min,r=0.9989.

关 键 词：二甲苯胺噻唑 羊 兔 药动-药效同步模型 兽药 

分 类 号：S859.79[农业科学—临床兽医学]