治疗癌症的双官能抗体－半抗原两步法的三房室药物动力学模型

Three-Compartment Pharmacokinetic Model of Two Step Approaches Using Bifunctional Antibody and Hapten for Cancer Therapy

近年来发明的生物疗法，如单克隆抗体（Ｍａｂｓ），增长因子（ＧＦＳ）等，它们在体外对癌细胞有很强的杀伤能力，但是由于肿瘤内部产生的生理屏障使药物很难到达肿瘤核心区，尤其是对于从人体免疫系统提取的像单克隆抗体这样的药物情况更为严重，因为免疫系统的细胞和分子比一般药物分子大得多。克服这些生理屏障的办法之一是采用具有高度特异性的小分子药物。最近引进的采用双官能抗体和小分子的半抗原的两步法在一定程度上满足了这个要求。本文采用三房室模型对治疗肿瘤的两步法进行了细致的药物动力学分析，并得到了一系列有实用价值的结果。三房室模型改进了已有的两房室模型￣［１］，使之更符合生理实际。

Various recently developed novel therapeutic agents , such as monoclonal antibodies(Mabs), growth factors(GFS)etc. have potent toxicity to cancer cells in vitro, but the physiological barriers in tumor make it difficult for these drugs to reach the tumor’s inner core , especially for the drugs drawn from the human im-mune system,likemonoclonal antibodies, because immune system cells and molecules are much larger than usual drug molecules, One strategy to Overcome these physiological barriers is to use low molecular weight agents with a high de-gree of specificity. A recently introduced approach satisfies this requirement to some extent:the use of low molecular weight haptens with bifunctional antibodies. Using three-compartment model, this paper provides a detailed parmacokinetic analysis of the two step approaches,and some valuable results are obtained,which improve pre-vious two-compartment model￣[1]and make it quantitively more accurate for cancer therapy.