摘要
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。
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.
出处
《中国肿瘤外科杂志》
CAS
2014年第3期166-169,共4页
Chinese Journal of Surgical Oncology
基金
广东省科技计划项目(2011B020800001)
广东省医学科研基金(B2010324)
东莞市科技计划项目(2010105150009)
关键词
5-氟尿嘧啶
肝癌
门静脉化疗
浓度
药动学
5-Fu
hepatocelluar carcinoma
portal venous chemotherapy
concentration
pharmaeokinetics
