持续静脉及动脉注射吡柔比星和表柔比星的药物代谢动力学比较

Comparison of pharmacokinetics of pirarubicin and epirubicin after continuous infusion through ear vein and interna iliac artery of rabbits

目的探讨吡柔比星(THP)和表柔比星(EPI)经动脉及静脉途径持续注射的体内变化规律和影响因素。方法40只成年新西兰雌兔随机均分为两组。THP组经髂内动脉或耳缘静脉持续注射THP 6 h,EPI组同法注射EPI。注射过程中于不同时间采集血样和子宫组织标本,注射完毕后,取心、肺和盆腔富含淋巴结的脂肪组织。以高效液相色谱法测定血清及各组织样本中的药物水平。结果THP动脉及静脉注射时血清中的药物峰水平分别为(0.12±0.05)和(0.16±0.10)μg/mL(P>0.05),子宫组织中药物水平的差异也无统计学意义(P>0.05)。动脉注射时,血清中THP的曲线下面积(AUC)值为0.47±0.15,约为静脉注射时的2/3(P>0.05),子宫组织中THP的AUC值为60.32±46.23,与静脉注射时基本相等(P>0.05)。EPI动脉及静脉注射时血清中药物峰水平分别为(0.13±0.07)和(0.23±0.13)μg/mL(P<0.05);子宫组织中药物水平的差异无统计学意义(P>0.05)。动脉及静脉注射EPI,血清中的AUC值分别为0.57±0.25及1.07±0.22(P<0.01),子宫组织中的AUC值分别为22.29±8.31和23.67±9.44(P>0.05)。动脉注射时,肺和心脏中的THP水平约为静脉注射时的1/2(P<0.01),EPI水平分别约为静脉注射时的1/3和1/2(P值均<0.05)。结论THP和EPI持续动脉注射时,靶器官中药物的分配略高于静脉注射,但未显示明显的优势;进入心脏组织的药物明显低于静脉注射。

Objective To explore the pharmacokinetics of pirarubicin and epirubicin （chemotherapeutic drugs） after continuous infusion via ear vein and internal iliac artery of rabbits. Methods Forty mature female New Zealand rabbits were randomly divided into two groups. Epirubicin was infused continually into the rabbits of first group via the ear vein or the internal iliac artery; each route of infusion included 10 animals. For the second group, epirubicin was given in the same manner as epirubicin. The blood samples and the uterus tissue specimens were collected at various time points during the infusion. At the end of infusion, the lung tissue, heart tissue and the fat tissue of pelvic were collected. The drug concentrations in the plasma and tissues were determined by HPLC methods. Results The peak serum concentrations of THP in the intra-arterial and intravenous group were （0.12±0.05） μg/mL and （0.16±0. 10） μg/mL, respectively （P〉0.05）. The levels of THP in uterine tissues were not significantly different between the 2 infusion route groups （P〉0.05）. The area under the curve （AUC） value of THP was 0.47±0.15 in serum for intra-arterial infusion group, which was about 2/3 that of intravenous infusion group （P〉0.05）. The AUC value of THP in uterine tissue was 60.32±46.23 in the intra-arterial infusion group, which was similar to that in the intravenous infusion group （P〉0.05）. The peak serum concentrations of EPI in intra-arterial and intravenous infusion group were （0.13±0.07） μg/mL and （0.23±0.13） μg/mL, respectively （P〈0.05）. The levels of EPI in uterine tissues were notsignificantly diffe rent （P〉0.05） ; the AUC values of EPI in serum were 0.57±0.25 and 1.07±0.22, respectively （P〈0.01） ;the AUC values of EPI in uterine tissues were 22.29±8.31 and 23.67±9.44, respectively （P〉0.05）. In the lung and heart tissues, the levels of THP at the end of intl：a-arterial infusion were about 1/2 of that at the end of intravenous infusion （P〈0.01）. The levels of EPI at the end of intra-arterial infusion were about 1/3 and 1/2 of those at the end of intravenous infusion （P〈0.05）. Conclusion Continous artery infusion of pirarubicin and epirubicin results in higher distribution in the target organs than venous infusion, but without significance. The dis tribution in the heart is lower than that of venous infusion.