5-氟尿嘧啶腹腔气雾化疗的药代动力学及组织分布

Pharmacokinetics and tissue distribution of intraperitoneal aerosol 5-fluorouracil in rats

目的观察5-氟尿嘧啶（5-Fu）以CO：为载体行腹腔气雾化疗的药代动力学及组织分布。方法将30只SD大鼠随机分为1、3、6、12、18、24h时间点组；用自行研制的气雾化疗仪将5-Fu气雾化后行腹腔灌注（0．1ml／g），在相应时间点抽取门静脉及下腔静脉血，取出结肠、胃、肝、肾及肺脏组织，用高效液相色谱法（HPLC）测定其中5．Fu浓度。结果腹腔液、门静脉及下腔静脉血，结肠、胃、肝、肾及肺脏组织中的药物浓度峰值均出现在1h组，药物浓度均随时间延长呈递减趋势；腹腔液中的药物浓度在1h组中达到峰值（259．7730mg／L）；在1h组中门静脉（PV）血中药物浓度浓度（7．4933mg／L）是下腔静脉（ICV，5．5930mg／L）的1．3倍；组织中肾脏浓度最高，1h组浓度为2．4030mg／L，肺、胃浓度次之，结肠、肝组织中浓度依次较低。结论5-Fu腹腔气雾化疗具有其药代动力学优势，有望有效杀灭游离癌细胞和微小癌灶。

Objective To study the pharmacokinetics and tissue distribution of intraperitoneal aerosol 5-fluorouracil （5-Fu） in rats. Methods Thirty SD rats were randomized into 1, 3, 6, 12, 18, 24 h time point groups; the 5-Fu （0. 1 ml/g） in aerosol was perfused into the abdominal cavities of rats with self-developed instrument. The blood of the portal vein and inferior vena cava, and samples of the colon, stomach, liver, kidney and lung were collected on the corresponding time points ; the concentrations of 5- Fu in the samples were determinated by using high performance liquid chromatography （HPLC）. Results The peak drug concentrations of the peritoneal fluid, blood of the portal vein and inferior vena cava, tissues of the colon, stomach, liver, kidney and lung all appeared in the 1 h group, and drug concentration was decreased along with time ; the peak drug concentration of peritoneal fluid in 1 h group was 259. 7730 mg/L. The peak drug concentration of portal vein blood in the 1 h group was 7. 4933 mg/L, about 1.3 times higher than that of inferior vena cava blood （5. 5930 mg/L）. Among the visceral organs, the peak drug concentration of renal tissue （2. 4030 mg/L） in 1 h group was highest, followed by that of the lung, stomach, colon, liver in turn. Conclusion Intraperitoneal aerosol chemotherapy with 5-Fu has pharmacokinetic advantages, which can kill free cancer cells and micro-cancers probably.