伊曲康唑固体脂质纳米粒在小鼠体内药动学和组织分布学

目的考察伊曲康唑固体脂质纳米粒在小鼠体内的靶向性.方法采用HPLC测定尾静脉注射给药后小鼠各组织中伊曲康唑浓度,比较伊曲康唑溶液和伊曲康唑固体脂质纳米粒在小鼠体内的药物动力学过程,来评价其靶向性。结果与ITZ溶液相比,ITZ-SLN的AUC是ITZ的2.23倍,t1/2β由45.511 h延长到69.315 h;肝中的相对摄取率re最大,达到5.055,;肝内总靶向效率Te从20.81%提高到41.74%。巨噬细胞丰富的脾脏、肺脏相对摄取率也分别达到了1.711和2.695。结论表明伊曲康唑固体脂质纳米粒生物利用度提高,药物在体内消除时间延长,可达到缓释长效的目的。ITZ制成ITZ-SLN后,体内靶向性发生了明显的改变,纳米粒有网状内皮系统靶向性。

Studies of pharmacokinetics and tissue distribution properties of ITZ-SLN in mice

Objective: To investegate the targeting of ITZ-SLN in mice.Methods: The drug concentrations in different tissues were determined by HPLC after intravenous administration in mice,and the targeting was evaluated by comparing the pharmacokinetic progresses in mice of ITZ-Sol and ITZ-SLN.Results: Compared with ITZ-Sol,the AUC of ITZ-SLN was 2.23 times of ITZ-Sol,and the eliminative half-life was prolonged from 45.511 to 69.315h.re of liver was the biggest and reached to 5.055,and Te of liver raised from 20.81% to 41.74%.The re of spleen and lung reached 1.711 and 2.965respectively.Conclusion: ITZ-SLN can improve the biological availability and prolong the elimination time in vivo to realize the delayed release.ITZ-SLN changes the targeting in vivo and nanoparticles are targeted to reticuloendothelial system.