盆腔封闭式循环化疗治疗妇科恶性肿瘤的实验研究

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。

Experimental study of pelvic cavity isolated circulation chemotherapy on treatment of gynecological malignant tumors

Objective:To explore the feasibility and pharmacokinetics change of pelvic cavity isolated circulation chemotherapy.Methods:10 dogs were divided into control group(4 dogs) and experimental group(6 dogs) randomly,control group underwent the procedure of routine internal iliac arterial infusion chemotherapy;experimental group received pelvic cavity isolated circulation chemotherapy and hemoperfusion,the chemotherapy medicine was carboplatin.The blood medicine concentrations of internal iliac vein and peripheral venous blood in two groups were measured,and the blood medicine concentration after hemoperfusion of experimental group.Results:The blood medicine concentrations of internal iliac vein in control group (5 497.71±601.8) ng/ml] and experimental group (5 151.19±558.6) ng/ml] reached the peak level on 10 minutes(P> 0.05).The blood medicine concentrations of internal iliac vein in control group decreased rapidly,(2 887.44±259.5) ng/ml on 20 minutes,(1 512.56±147.9) ng/ml on 30 minutes,(889.87±92.4) ng/ml on 40 minutes,(733.76±72.08) ng/ml on 50 minutes,(571.46±315.76) ng/ml on 60 minutes;the blood medicine concentrations of internal iliac vein in experimental group still maintained the high level,(5 121.31±530.2) ng/ml on 20 minutes,(4 998.57±511.4) ng/ml on 30 minutes,(4 018.3±378.9) ng/ml on 40 minutes,(2 894.47±285.0) ng/ml on 50 minutes,(2 114.18±189.7) ng/ml on 60 minutes,the blood medicine concentrations of every time intervals in two groups had significant difference(P<0.01).There was significant difference in AUC between control group (110 943.021±9 056.78) ng/ml·min] and experimental group (229 430.114±2 154.07) ng/ml·min](P<0.01).The blood medicine concentrations of peripheral venous blood in control group were(4 984.94±468.8) ng/ml on 10 minutes,(3 387.83±325.7) ng/ml on 20 minutes,(1 312.48±126.6) ng/ml on 30 minutes,(1 089.59±97.7) ng/ml on 40 minutes,(771.07±73.5) ng/ml on 50 minutes,(521.33±48.3) ng/ml on 60 minutes;while the blood medicine concentrations of peripheral venous blood in experimental group were(20.54±2.4) ng/ml on 10 minutes,(37.01±3.5) ng/ml on 20 minutes,(50.99±4.8) ng/ml on 30 minutes,(88.63±9.1) ng/ml on 40 minutes,(125.72±12.8) ng/ml on 50 minutes,(134.88±12.3) ng/ml on 60 minutes,there was significant difference(P<0.01).The clearance rate of the blood medicine in experimental group after hemoperfusion was(92.71±7.7)%.Conclusion:Compared with routine internal iliac arterial infusion chemotherapy,pelvic cavity isolated circulation chemotherapy is one kind of feasible technology,which not only increases the partial blood medicine concentration in a long time,but also reduces the peripheral blood medicine concentration,reduces the poisonous side effect.