低温环境下容量控制性失血性休克猪的丙泊酚药代动力学研究

Pharmacokinetics of propofol in pigs with volume controlled hemorrhagic shock in hypothermic environment

目的探讨低温环境下容量控制性失血性休克猪体内丙泊酚药代动力学的特点。方法24头健康巴马小型猪,应用随机数字表法将其随机分为4组,每组6头,分别为常温不休克组(C组)、常温休克组(CS组)、低温不休克组(D组)、低温休克组(DS组)。建立低温失血性休克模型,四组均静脉泵入丙泊酚200μg/(kg·min)共10 min。在静脉泵入丙泊酚0、4、8、10、11、12、13、14、15、17.5、20、25、30、45、60、180 min时,测定丙泊酚血浆药物浓度。根据已测定的血药浓度计算丙泊酚的消除半衰期(t_(1/2))、血浆-效应室平衡速率常数(K_(e0))、药时曲线面积(AUC)及平均驻留时间(MRT)等药代动力学参数。结果丙泊酚血药浓度:D组与C组比较,差异有统计学意义(P<0.05);DS组与CS组、D组比较,差异有统计学意义(P<0.05)。最大药物浓度(C_(max)):D组高于C组,DS组高于CS组、D组,差异均有统计学意义(P<0.05)。t_(1/2):D组较C组延长,DS组较CS组、D组延长,差异均有统计学意义(P<0.05)。MRT:D组较C组延长,DS组较CS组、D组延长,差异均有统计学意义(P<0.05)。K_(e0)、AUC:D组和CS组略高于C组,但差异无统计学意义(P>0.05);DS组略高于D组、CS组,差异无统计学意义(P>0.05)。结论低温环境下容量控制性失血性休克猪丙泊酚的药代动力学特点是代谢减慢,药物的消除半衰期延长,血浆-效应室平衡速率常数增大,体内平均驻留时间延长。

Objective To investigate the pharmacokinetics characteristics of propofol in pigs with volume controlled hemorrhagic shock in hypothermic environment.Methods Twenty-four Bama mini pigs were randomly divided into 4 groups：group C（pigs without hemorrhagic shock at room temperature）,g roup CS（pigs with hemorrhagic shock at room temperature）,g roup D（pigs without hemorrhagic shock at low temperature）,group DS（pigs with hemorrhagic shock at low temperature）.The hypothermia hemorrhagic shock models were established.Propofol 200 μg/（kg·min）was infused for 10 min;5 mL venous blood was collected before administration of propofol and at 2,4,6,8,10,11,12,13,14,15,17.5,20,25,30,45,60,180 min after infusion,and the concentration of propofol was analyzed by high performance liquid chromatography fluorescence（HPLC-fluorescence）.SPSS was used to calculate the elimination half-life（t_（1/2））of propofol,the plasma-effect site equilibration rate content（K_（e0））,the drug＇s area under the curve（AUC）,the mean residence time（MRT）and the other pharmacokinetic parameters.Results At 10 ~ 60 min after infusion,the plasma concentration of propofol in group D was higher than that of group C,and the concentration in group DS was higher than that of group CS（P〈0.05）.Cmax in group D was higher than that of group C,and the index in group DS was higher than those of group CS and group D,there being significant differences（P〈0.05）.The t_（1/2） and MRT in group D was longer than that of group C,and the indexes in group DS were longer than those of group CS and group D,there being significant differences（P〈0.05）.The K_（e0） and AUC in group D and group CS were slightly higher than those of group C,and the indexes in group DS were slightly higher than those of group D and group CS,but there was no significant difference（P〉0.05）.Conclusion The pharmacokinetics characteristic of propofol in pigs with volume controlled hemorrhagic shock in hypothermic environment is manifested as slower metabolism,longer elimination half-life,increased K_（e0） and longer MRT.