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目的:探讨盆腔封闭式循环化疗的可行性及药代动力学变化。方法:将10只犬随机分为2组,对照组4只,行常规髂内动脉灌注化疗;实验组6只,行经皮盆腔封闭式循环化疗(化疗药物选用卡铂)结合血液灌流。定时检测两组髂内静脉、外周血液的血药浓度及实验组血液灌流后的血药浓度。结果:对照组和实验组髂内静脉血药浓度均在10 min达峰值,分别为(5 497.71±601.80)ng/ml、(5 151.19±558.60)ng/ml,两组比较无统计学差异(P>0.05)。对照组20 min、30 min、40min、50 min、60 min血药浓度迅速下降,分别为(2 887.44±259.50)ng/ml、(1 512.56±147.90)ng/ml、(889.87±92.40)ng/ml、(733.76±72.80)ng/ml、(571.46±47.60)ng/ml;而实验组仍保持较高浓度,分别为(5 121.31±530.20)ng/ml、(4998.57±511.40)ng/ml、(4 018.30±378.90)ng/ml、(2 894.47±285.00)ng/ml、(2 114.18±189.70)ng/ml,两组各时段血药浓度比较有统计学差异(P<0.01)。两组药时曲线下面积(AUC)分别为(110 943.02±9 056.78)(ng/ml.min)、(229430.11±2 154.07)(ng/m.min),有统计学差异(P<0.01)。对照组10 min、20 min、30 min、40 min、50 min、60 min外周血药浓度分别为(4 984.94±468.80)ng/ml、(3 387.83±325.70)ng/ml、(1 312.48±126.60)ng/ml、(1 089.59±97.70)ng/ml、(771.07±73.50)ng/ml、(521.33±48.30)ng/ml,实验组分别为(20.54±2.40)ng/ml、(37.01±3.50)ng/ml、(50.99±4.80)ng/ml、(88.63±9.10)ng/ml、(125.72±12.80)ng/ml、(134.88±12.30)ng/ml,两组比较有统计学差异(P<0.01)。实验组血液灌流后的血药清除率为(92.71±7.70)%。结论:盆腔封闭式循环化疗是一种可行的技术,与常规髂内动脉灌注化疗相比,不仅可以在较长时间内增加局部血药浓度,还可以降低外周的血药浓度,减少毒副作用。
Objective: To investigate the feasibility and pharmacokinetic changes of pelvic closed-cycle chemotherapy. Methods: Ten dogs were randomly divided into two groups. Four rabbits in the control group received routine internal iliac arterial infusion chemotherapy. Six rabbits in the experimental group received percutaneous pelvic closed-cycle chemotherapy combined with carboplatin chemotherapeutics combined with hemoperfusion. The two groups of internal iliac vein were measured regularly, the blood concentration of peripheral blood and the blood concentration of the experimental group after blood perfusion. Results: The plasma concentrations of iliac vein in control group and experimental group reached the peak at 10 min, which were (5 497.71 ± 601.80) ng / ml and (51 151.19 ± 558.60) ng / ml, respectively. There was no significant difference between the two groups P> 0.05). The blood concentration of control group decreased rapidly at 20 min, 30 min, 40 min, 50 min and 60 min, respectively (8887.44 ± 259.50) ng / ml, (1 512.56 ± 147.90) ng / ml and (889.87 ± 92.40) ng / ml, (733.76 ± 72.80) ng / ml and (571.46 ± 47.60) ng / ml, respectively, while the experimental group remained at higher concentrations (5 121.31 ± 530.20 ng / ml, 4998.57 ± 511.40 ng / ml, (4 018.30 ± 378.90) ng / ml, (2 894.47 ± 285.00) ng / ml and (2 114.18 ± 189.70) ng / ml respectively. There was a significant difference in plasma concentration between the two groups (P <0.01). The area under curve (AUC) of the two groups were (110 943.02 ± 9 056.78) ng / ml.min and 229430.11 ± 2 154.07 ng / m.min, respectively, with statistical difference (P 0.01) . The peripheral blood concentrations of control group were (984.94 ± 468.80) ng / ml, (3 387.83 ± 325.70) ng / ml, (1212.48 ± 126.60 (20.54 ± 2.40) ng / ml, (37.01 ± 3.50) ng / ml, (1 089.59 ± 97.70) ng / ml, (771.07 ± 73.50) ng / ml and (521.33 ± 48.30) (P <0.05). There was a significant difference between the two groups (P <0.05), (50.99 ± 4.80) ng / ml, (88.63 ± 9.10) ng / ml, (125.72 ± 12.80) ng / ml and (134.88 ± 12.30) ng / <0.01). The blood clearance rate of the experimental group after blood perfusion was (92.71 ± 7.70)%. Conclusion: Closed-loop pelvic chemotherapy is a feasible technique. Compared with conventional intra-arterial infusion chemotherapy, it can not only increase local blood concentration for a long time, but also reduce peripheral blood concentration and reduce side effects.