【摘要】 目的研究球形实体肿瘤中生理参数对药物输运的影响,以及探讨有较好效果的药物注射方式。方法设肿瘤中毛细血管网成球对称分布,肿瘤中的毛细血管表面积和肿瘤体积之比为半径的函数。肿瘤间质为多孔介质,化学药物透过毛细血管壁进入肿瘤间质,在肿瘤间质中输运满足扩散方程。肿瘤外正常组织富含血管和淋巴,药物能被淋巴管吸收,药物输运采用改进的药代动力学模型。用肿瘤中各部位药物浓度维持在最小药物浓度MEC水平以上的时间曲线面积(AUC)来衡量药物的效果。结果增大肿瘤间质中毛细血管对药物的通透性P,提高药物在肿瘤间质的扩散系数D,AUC的值均增大。在给出的六种给药方式中,分时段连续滴注和等时间间隔一次性注射的给药方式,它们的AUC值最大。结论增大肿瘤间质中毛细血管对药物的通透性,提高药物在肿瘤间质的扩散系数,以及采用分时段连续滴注和等时间间隔一次性注射的给药方式,有利于肿瘤的治疗。更多还原

【Abstract】 Objective To investigate the effect of physiology parameter and drug injection-methods on drug delivery in solid tumor. Methods The distributing of the tumor vascular is sphere-symmetry, and the surface areas per unite volume for blood vessels is a function of radius. The tumor interstitium is considered as porous medium and drug could pass through the microvascular into it. The drug in tumor interstitium is transported by diffusion. The interstitium of normal tissue contain vessels and lymphatic, and the drug can be absorbed by lymphatic. In the normal tissue an advanced pharmacokinetic model is considered. The area under the curve (AUC) of drug concentration which is higher than minimum effective concentration (MEC) in tumor during 24 hours is used to evaluate the treatment of drug. Results Increasing vascular permeability coefficient P and the drug diffusion coefficient D, AUC will increase. In the six injection-methods, injecting by continuing-dropping in separated time periods or bolus injection in several times with the same interval could obtain the highest AUC. Conclusion Increasing vascular permeability coefficient, raising the drug diffusion coefficient, and injecting by continuing-dropping in separated time periods or bolus injection in several times with the same interval are more useful for treatment of tumor.更多还原