球形和扁球肿瘤双功能抗体和与酶结合的抗体两步法的双重介质模型药物动力学分析  

DOUBLEMEDIUM PHARMACOKINETIC ANALYSIS OF TWOSTEP APPROACHES IN SPHERIC AND OBLATE SPHERIC TUMOR USING BIFUNCTIONAL ANTIBODIES AND ENZYMECONJUGATED FORCANCER DIAGNOSIS AND THERAPY

作　　者：许扬清[1] 温功碧[1] 

机构地区：[1]北京大学力学和工程科学系

出　　处：《中国生物医学工程学报》1998年第3期199-207,共9页Chinese Journal of Biomedical Engineering

摘　　要：由于恶性肿瘤内部存在生理屏障，药物很难到达肿瘤核心区，给诊断和治疗带来了困难。具有高度特异性的小分子药物的两步法在一定程度上克服了这一问题。本文对于球形和扁球肿瘤，采用包括血浆和组织液的双重介质分布参数模型，对双功能抗体ＢＦＡ（Ｂｉｆｕｎｃｔｉｏｎａｌａｎｔｉｂｏｄｉｅｓ）－半抗原（Ｈａｐｔｅｎ）和与酶结合的抗体ＥＣＡ（Ｅｎｚｙｍｅ－ｃｏｎｊｕｇａｔｅｄａｎｔｉｂｏｄｉｅｓ）－前药物（Ｐｒｏｄｒｕｇ）两套系统进行了两步法的药物动力学分析。结果表明，两步法可以在一定程度下改善肿瘤中心区药物灌注不良的状况。本文详细分析了注射方式与剂量、注射时间的影响，以及肿瘤内药物浓度分布对药物动力参数、化学反应常数等的敏感性，并对比了ＢＦＡ系统和ＥＣＡ系统的异同。此外，还对比了扁球肿瘤中的压力分布和药物分布。hysiological barrier exsiting in malignant tumor prevented medicine molecule to reach the inner core of tumor, thereby it was difficult to diagnose and treat the tumor. Twostep approaches using low molecular weight agents with high specificity surmounted this difficulty to some extent, and we provided a detailed pharmacokinetic analysis of twostep approaches in spheric and oblate spheric tumors using bifunctional antibodies and enzymeconjugated ones with bloodtissue doublemedium model. We analysed the effect of the way, dose and time schedule of injection, and the sensibility of the distribution of medicine to the dynamical and reactive coefficients; then we compared the BFA system with the ECA system, as well as the distribution of pressure and medicine in oblate spheric tumor; and finally, based on these results, some clinical suggestion on tumor diagnosis and therapy were given.

关 键 词：双功能抗体 半抗原两步法 药物动力学 

分 类 号：R979.1[医药卫生—药品] R912[医药卫生—药学]