Comparative study of concentrations of antitumor agents in serum and tumor in nude mouse and human

裸鼠与人的药代动力学比较，对于将人肿瘤移植瘤-裸鼠系统作为新型抗肿瘤药物的筛选平台具有重要意义。以最大耐受剂量的丝裂霉素C（MMC）、阿霉素（ADM）、5-氟尿嘧啶（5-FU）、顺铂（DDP）、DWA 2114 R（DWA）和卡铂（CBDCA）对荷人肿瘤裸鼠进行给药，并以临床常用剂量对患者进行给药。MMC、5-FU采用生物活性测定法，ADM采用高效液相色谱法，DDP、DWA、CBDCA采用原子吸收法，测定血清及肿瘤组织中抗癌药物浓度，（Cmax，ug/ml）和肿瘤中的浓度在裸鼠和人中的T（以μ g/g计）如下：mmc ADM 5-FU DDP DWA CBDCA小鼠Cmax 1.09 1.44 44.7 4.8 30.3 61.2人Cmax 0.84 0.42 85.4 2.2 24.0 6.5 T/Cmax%（小鼠）1.3 209.1 10.4 40.6 31.0 27.9 T/Cmax%（人体）0.9 354.6 3.1 42.9 30.7 10.4小鼠和人体中每种药物的T/Cmax比值相似，具有统计学显著性，r = 0.996（p 0.001）。

The pharmacokinetic comparison between nude mouse and human beings is important to use the human tumor xenografts - nude mouse system as a screening panel of newly developed antiunor agents. Mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU), cisplatin (DDP), DWA2114R (DWA) and carboplatin (CBDCA) were administered to nude mice bearing human tumor xenografts in maximum tolerated doses and to patinets with cancer in conventionally available doses in clinics. The concentrations of antitumor agents in serum and tumor were detected by bioassay for MMC and 5-FU, high performance liquid chromatography for ADM and atom absorption method for DDP, DWA and CBDCA.The maximum serum concentration (Cmax in ug/ml) and concentration in tumor (T in ug/g) in nude mouse and human were as follows; mmc ADM 5-FU DDP DWA CBDCA Cmax in mouse 1.09 1.44 44.7 4.8 30.3 61.2 Cmax in human 0.84 0.42 85.4 2.2 24.0 6.5 T/Cmax% (mouse) 1.3 209.1 10.4 40.6 31.0 27.9 T/Cmax% (human) 0.9 354.6 3.1 42.9 30.7 10.4 T/Cmax ratio of each agent in mouse and human was similar to each other with a statistical significance at r = 0.996 (p 0.001).