实体肿瘤药物输运与给药方式的集中参数模型及实验研究

目的研究不同给药方式对实体肿瘤抗癌药物疗效的影响,并通过动物实验验证。方法分别建立体内药代动力学和肿瘤内药物输运的集中参数模型,模拟单次快速注射和等时间间隔三次快速注射时肿瘤间质组织药物浓度Ct随时间的变化。实验小鼠分为两组,分别进行抗癌药羟基喜树碱(HCPT)单次快速注射和等时间间隔3次快速注射,观察其肿瘤内药物平均浓度。对数值模拟结果和动物实验结果进行比较。结果数值模拟结果显示,对于相同总量药物,等量等间隔的三次给药,肿瘤间质组织药物浓度Ct高于单次给药。动物实验的实测结果相同。结论3次给药的效果显著优于单次给药。集中参数模型基本能够定量反映不同给药方式的效果。

Effect of drug dosing regiments on drug delivery in solid tumor by lumped parameter modeling and animal experiments

Objective To investigate effects of dosing regiment on drug delivery in solid tumor via Lumped parameter modeling, and to validate them with experiment on rats. Methods Lumped parameter Models of pharmacokinetic and of drug delivery in tumor were developed, to simulate time courses of average drug concentration (tC) in tumor interstitium with two types of injection-methods (single-shot and trio-shot). The same performance was also made in rats experiment with two groups by given HCPT. Result It showed by lumped parameter modeling that trio-shot method is more efficacious than single-shot method and also validated by the experimental data from the rats test.C onclusion Trio- shot injection is more effective than single-shot injection. The present lumped-parameter model is quantitatively competent for the effect of different drug delivery on solid tumor.