羟基喜树碱脂肪乳在大鼠体内的药动学及组织分布研究

Pharmacokinetics and Tissue Distribution of Hydroxycamptothecin Lipid Emulsion in Rats

目的:研究羟基喜树碱(HCPT)脂肪乳在大鼠体内的药动学及组织分布。方法:采用高效液相色谱法测定静脉注射HCPT脂肪乳后大鼠血浆及组织中HCPT浓度,计算药动学参数并分析药物在组织中的分布情况,并与静脉注射HCPT溶液比较。结果:HCPT脂肪乳和溶液在大鼠体内药动学过程呈二室吸收模型,t1/2α分别为(0.081±0.011)h、(0.517±0.721)h,t1/2β分别为(0.778±0.107)h、(0.3890±0.053)h,AUC(0～4h)分别为(1.619±0.223)μg·h·mL-1、(2.031±0.280)μg·h·mL-1,Cl(S)分别为(114.3±15.7)mL·h-1、(100.3±13.8)mL·h-1;与溶液比较,静脉注射HCPT脂肪乳后HCPT在肝、肺、脾、脑中的浓度更高。结论:与HCPT溶液剂型比较,脂肪乳剂型更能提高药物对肝、肺、脾、脑的趋向性。

OBJECTIVE： To study the pharmacokinetics and tissue distribution of hydroxycamptothecin （HCPT） lipid emulsion in rat. METHODS： The contents of HCPT in rat plasma and tissues were determined by HPLC. After medication of HCPT lipid emulsion, the pharmacokinetic parameters were calculated and the distribution of HCPT lipid emulsion （i.v.） was analyzed to compare with those after medication of HCPT solution （i.v.）. RESULTS： The plasma concentration-time curves of HCPT fitted to two-compartment model. The main pharmacokinetic parameters of HCPT lipid emulsion vs. HCPT solution were as follows： t1/2α ： （0.081 ±0.011） h vs. （0.517±0.721） h; t1/2β （0.778±0.107） h vs. （0.389 0±0.053） h; AUC（0-4h）： （1.619±0.223） μg·h· mL^-1 vs. （2.031 ± 0.280） μg·h· mL^-1; Cl（s） ： （114.3± 15.7） mL·h^-1 vs. （100.3 ± 13.8） mL·h^-1. The concentration of HCPT in liver, lung, spleen and brain after medication of HCPT lipid emulsion （i.v.） were higher than those after medication of HCPT solution （i. v.）. CONCLUSION： The HCPT lipid emulsion can increase the targeting effect of HCPT to liver, lung, spleen and brain, as compared with HCPT solution.