区域性灌注化疗时5-FU的血液和肝脏组织药物浓度分布特征

Distribution of 5-FU in rat plasma and liver tissue after local 5-FU infusion

目的研究经肝动脉和门静脉等不同途径区域灌注化疗时5-FU在大鼠血液和肝脏组织中的浓度分布和消除过程,为临床肝脏肿瘤化疗提供参考。方法经颈静脉注射5-FU或分别经肝动脉及门静脉插管区域灌注,剂量为20mg/kg体重。采用高效液相色谱法测定血浆及肝脏组织中5-FU的含量。进一步计算5-FU在肝脏和血浆中的药动学数据和穿透比率及治疗优势度。结果外周静脉注射时,肝脏组织的药物峰浓度(Cmax)和药物时量曲线下面积(AUC)分别为13.79±4.56μg/g,342.20±108.20μg·min/g;血浆Cmax和AUC分别为36.85±5.96μg/ml,842.00±158.00μg·min/ml。肝动脉灌注5-FU时,肝脏组织药物Cmax和AUC分别为29.58±4.30μg/g,794.60±115.40μg·min/g;血浆Cmax和AUC分别为24.39±4.63μg/ml,639.70±133.80μg·min/ml。门静脉灌注时,肝脏组织药物Cmax和AUC分别为28.21±4.46μg/g,733.60±180.3μg·min/g;血浆Cmax和AUC分别为21.02±4.06μg/ml,529.80±111.50μg·min/ml。结论与外周静脉注射全身化疗比较,区域性肝动脉或门静脉灌注化疗可显著提高肝脏组织中的药物浓度,同时减少化疗药物在外周血中的分布,可作为临床肝癌化疗的较好治疗措施。

Objective TO study the distribution of 5-FU in rat plasma and liver tissue following systemic or local 5-FU infusion. Methods 5-FU was administered at the dose of 20 mg/kg systemically via bolus injection through the jugular vein or locally via infusion through the hepatic artery and portal vein of the rats. High-performance liquid chromatography was used to measure 5-FU concentration in the plasma and liver tissue, and the pharmacokinetic parameters, penetration rate and therapeutic dominance of 5-FU were calculated. Results Systemic administration of 5-FU resulted in the peak 5-FU concentration （Cmax） and area under curve （AUC） in the liver tissue of 13.79±4.56 μg/g and 342.20±108.20 μg·min^-1·g^-1 with the plasma Cmax and AUC of 36.85±5.96 μg/ml and 842.00±158.00 μg·min^-1·g^-1 repsecitvely. Local 5-FU administration through the hepatic artery resulted in Cmax and AUC in the liver tissue of 29.58±4.30 μg/g and 794.60±115.40 μg·min^-1·g^-1and Cmax and AUC in the plasma of 24.39±4.63 μg/ml and 639.70±133.80 μg·min^-1·g^-1 respectively, After administration through the portal vein, the Cmax and AUC of 5-FU was 28.21±4.46 μg/g and 733.60± 180.3 μg·min^-1·g^-1in the liver tissue, and 21.02±4.06 μg/ml and 529.80±111.50 μg·min^-1·ml^-1 in the plasma, respectively. Conclusion Compared with systemic venous bolus injection, administration through the hepatic artery and portal vein can significantly increase 5-FU concentration in the liver, and decrease its concentration in the peripheral blood.