5-氟尿嘧啶磁性白蛋白亚微球在正常及荷瘤小鼠体内的药代动力学与组织分布

Pharmacokinetics and distribution of 5-Fu magnetic albumin deuto-microsphere in normal and tumor-bearing mice

5-氟尿嘧啶磁性白蛋白亚微球(5-flourouracilmagneticalbumindeuto-microsphere,5-Fu-MAD)是新型靶向给药系统,考察正常及荷瘤小鼠体内的代谢和分布为其临床应用提供参考。采用HPLC方法测定生物样品中5-Fu浓度。采用原子吸收光谱法测定组织铁浓度。结果显示,小鼠尾静脉注射5-Fu原料药及5-Fu-MAD后,于不加或加磁性支架条件下,药代动力学过程均呈一级二室动力学模型。小鼠静脉注射5-Fu各制剂组后5-Fu和Fe的分布以肝脏、肿瘤组织、脾脏、肺脏为高,肾脏、心脏次之,脑组织和肌肉组织最低。正常小鼠的肌肉组织和荷瘤小鼠肿瘤组织给予磁性支架后,分布显著增加(P<0.01)。可见,5-Fu-MAD在小鼠体内的分布具有缓释特征,且对加入了磁性支架的组织具有靶向性。

To observe the pharmacokinetic and tissue-distribution characters of 5-flourouracil magnetic albumin deuto-microsphere （5-Fu-MAD） in normal and tumor-bearing mice, HPLC method for the determination of 5-Fu in plasma and tissues was established and applied to determine 5-Fu in mouse plasma and tissue samples. A Flame atomic absorption spectrometer was used to detect the iron concentration in mouse tissue. Plasma concentration-time curves of free 5-Fu, 5-Fu-MAD and 5-Fu-MAD plus the magnetic frame （MF） conformed to two compartment model of first order absorption and they had Cx of 34.9, 7.95 and 5.97 mg·L^-1; T1/2（Ke） of 22.26, 76.0 and 124.6 min, Vd of 3.28, 30.7 and 66.1 L·kg; AUC0-6 of 233.9, 78.3 and 50.2 mg·min·L^-1; AUC0-∞ of 237.2, 89.3 and 68.1 mg·min·L^-1, respectively. The distribution of 5-Fu and iron was the highest in the plenty blood perfusion organs like the liver, tumor, spleen and lung, while lower in the kidney and heart and lowest in brain and muscle. The tissue distribution of muscle and tumor increased significantly when a magnetic frame was inserted there. The pharmacokinetics and tissue distribution of 5-Fu-MAD exhibited sustainedrelease and target characteristics.