经门静脉途径灌注化疗时5-Fu在肝脏和血液中的浓度和药动学特点

目的研究经门静脉途径灌注化疗时5-Fu在肝脏和血液中的浓度和药动学特点,并与外周静脉注射化疗相比较,探讨区域性门静脉灌注化疗的优势。方法 24只Wistar大鼠随机分组后分别经门静脉插管区域灌注及经外周静脉注射5-Fu,剂量均为20 mg/kg。采用高效液相色谱法(HPLC)测定两组给药后5、10、20、30、45、60、90、120、180 min不同时间点血浆和肝脏组织中5-Fu的浓度,对比两组5-Fu在肝脏和血浆中的药动学数据。对比两组的穿透比率、穿透指数及治疗优势度。结果经外周静脉注射5-Fu时,肝脏组织中的药物峰浓度(Cmax)和药物时量曲线下面积(AUC)分别为(13.79±4.56)μg/g及(342.20±108.20)μg·h/ml;血浆中的Cmax和AUC分别为(36.85±5.96)μg/g及(842.00±158.00)μg·h/ml。经门静脉灌注时,肝脏组织中的Cmax和AUC分别为(28.21±4.46)μg/g及(733.60±180.30)μg·h/ml;血浆中的Cmax和AUC分别为(21.02±4.06)μg/g及(529.80±111.50)μg·h/ml。门静脉灌注化疗与外周静脉注射相比的治疗优势度为3.37。结论与外周静脉注射全身化疗比较,区域性门静脉灌注5-Fu化疗可显著提高肝脏组织中的药物时-量作用强度,同时减少化疗药物在外周血中的分布,可作为肝癌化疗有效的给药途径

5-Fu concentration and its pharmacokinetics in rat plasma and liver tissue through loco-regional portal venous infusion

Objective To explore the concentration and pharmacokinetics of 5-Fu in rat plasma and liver tissue through loco-regional portal venous route. Methods To fulfill the systemic venous injection, jugular vein was catheterized, and the portal vein was catheterized to infuse 5-Fu, too. The dose was 20 mg/kg and HPLC was adopted to measure the content of 5-Fu in rat plasma and liver tissue. Thus the pharmacokinetics parameters were calculated and compared. Results Through the systemic vein route, the peak concentration（Cmax） and fime-quality area under curve （AUC） of liver tissue were as follows： （13. 79 ± 4. 56） μg/g, （342. 20 ± 108.20） μg · h/ml, and the plasma Cmax and AUC were （36.85 ± 5.96） μg/g, （842.00 ± 158.00） μg · h/ ml. Through portal vein route, the Cmax and AUC of liver tissue were （28.21 ± 4.46） μg/g, （733.60 ＋ 180.30） μg · h/ml, and the Cmax and AUC of plasma were （21.02 ±4.06） μg/g, （529.80 ± 111.50） μg · h/ml. Conclusions Comparing to systemic venous bolus injection, portal vein infusion can increase the concentrations of chemotherapy agent significantly, and the drug distributions decrease in peripheral blood plasma.