摘要
目的探讨缩宫素在妊娠晚期及剖宫产术后大鼠体内药代动力学变化的特点,为缩宫素的临床应用提供参考。方法SPF级SD大鼠36只随机分成6组,每组6只。A、B、C组为妊娠晚期组,分别单次尾静脉注射0.1、0.5、5 U/kg的缩宫素;D、E、F组为剖宫产术后组,行剖宫产术后分别单次尾静脉注射0.1、0.5、5 U/kg的缩宫素。6组大鼠分别于给药后1、2、4、6、8、10、15、20、45、60 min采血。采用高效液相色谱-二级质谱联用(high performance liquid chromatography-mass spectrometry,HPLC-MS/MS)的方法测定缩宫素的血药浓度结果,计算缩宫素在大鼠体内的消除半衰期(T_(1/2))、药时曲线面积(area under the drug concentration time curve,AUC)、平均驻留时间(mean residence time,MRT)、表观分布容积(apparent volume of distribution,Vd)和血浆清除率(plasma clearance,CL)等药代动力学参数。统计学方法采用方差分析。结果①在0.01-300 U/L范围,缩宫素血药浓度与峰面积具有良好的线性关系,回归方程为y=1143.36 x+8.78(R^(2)=0.9983)。血浆样品提取回收率较高。②妊娠晚期的A、B、C组给予缩宫素后,血药浓度迅速升高,各时间点3组间比较差异有统计学意义(P<0.05);与A组相比,B组和C组T_(1/2)明显缩短(P<0.05);与A、B组相比,C组MRT亦明显缩短(P<0.05);与A组相比,C组CL显著增加(P<0.05);3组AUC比较差异有统计学意义(P<0.05),随着给药浓度的增高,AUC呈现递增趋势。③剖宫产术后的D、E、F组给予缩宫素后,最大浓度时间(maximum concentration,T_(max))均为给药后1 min;3组间最大浓度(maximum concentration,C_(max))比较差异有统计学意义(P<0.05);与D组相比,E组和F组T_(1/2)明显缩短(P<0.05);与D、E组相比,F组的MRT亦明显缩短(P<0.05);与D组相比,F组CL显著增加(P<0.05);3组AUC比较差异有统计学意义(P<0.05),随着给药浓度的增加,AUC呈现递增趋势。结论缩宫素在妊娠晚期及剖宫产术后大鼠体内的半衰期为7-10 min,达峰时间为1 min,缩宫素的最佳给药方式是持续静脉滴注给药;同时,随着给药浓度的增加,缩宫素在大鼠体内代谢加快,T_(1/2)、MRT变短,Vd、CL和AUC增加。
Objective To explore the effects of oxytocin in pharmacokinetic changes in the late pregnancy and cesarean section rats,for the clinical application of oxytocin.Methods 36 SPF grade SD rats were randomly divided into 6 groups,6 rats in each group.A,B,C three groups were late pregnancy rats intravenously given 0.1,0.5,5 U/kg of oxytocin.D,E,F groups were cesarean section rats given by tail channels 0.1,0.5,5 U/kg of oxytocin.All the rats were collected blood at 1,2,4,6,8,10,15,20,45,60 min after injection.We use the high performance liquid chromatography-mass spectrometry(HPLC-MS/MS)to detect the plasma concentration of oxytocin.The pharmacokinetic parameters such as half-life(T_(1/2)),area under the drug concentration time curve(AUC),mean residence time(MRT),apparent volume of distribution(Vd)and plasma clearance(CL)of oxytocin were calculated according to the plasma concentration which has been measured.Statistical analysis were used with analysis of variance.Results①In the range of 0.01-300 U/L,oxytocin plusm concentration and peak area had good linear relationship,and the regression equation was y=1143.36x+8.78(R^(2)=0.9983).The plasma samples extraction recovery rate was high.②In the late pregnancy group,the plasma concentration increased after injection.There were significantly differences among group A,B and C(P<0.05).Compared with group A,T_(1/2) of group B and C were shorter(P<0.05).Compared with group A and B,the MRT of group C was also significantly shorter(P<0.05).Compared with group A,the CL of group C increased significantly(P<0.05).AUC of three groups had significantly differences(P<0.05).With the increase of drug concentration,AUC showed an increasing trend.③After injection of oxytocin,the T_(max) of group D,E and F were 1 min after injection.The maximum concentration(C_(max))of the three groups had significant differences(P<0.05).Compared with the group D,T_(1/2) of group E and F were significantly shorter(P<0.05).Compared with group D and E,MRT of group F was also significantly shorter(P<0.05).Compared with group D,the CL of group F increased significantly(P<0.05).AUC of the three groups had significantly differences(P<0.05).As the concentration increased,AUC showed an increasing trend.Conclusions The half-life of oxytocin is about 7-10 min in the late pregnancy and cesarean section rats,and the peak time is 1 min.The best way of administration of oxytocin is continuous intravenous drip.At the same time,with the increase of oxytocin concentration,the metabolism of oxytocin accelerates.T_(1/2) and MRT shorten,while Vd,CL and AUC increase.
作者
刘婷婷
曲冬颖
Liu Tingting;Qu Dongying(Department of Obstetrics and Gynecology,Heping Branch,Northern Theater General Hospital,Liaoning,Shenyang 110001,China)
出处
《发育医学电子杂志》
2022年第1期31-37,69,共8页
Journal of Developmental Medicine (Electronic Version)
基金
辽宁省科学技术计划项目(2021JH2/10300095)。
关键词
孕鼠
剖宫产
缩宫素
高效液相色谱-二级质谱联用
药代动力学
Pregnant rats
Cesarean section
Oxytocin
High performance liquid chromatography-mass spectrometry
Pharmacokinetics
