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

裸鼠和人的药代动力学比较对于利用人肿瘤移植瘤-裸鼠系统作为新开发的抗肿瘤药物的筛选小组具有重要意义。临床应用丝裂霉素C(MMC)、阿霉素(ADM)、5-氟尿嘧啶(5-FU)、顺铂(DDP)、DWA2114R(DWA)和卡铂(CBDCA)治疗荷人肿瘤裸鼠和常规剂量的癌症患者。采用MMC和5-FU生物测定法、ADM高效液相色谱法和原子吸收法检测血清和肿瘤组织中抗肿瘤药物的浓度。裸鼠和人的最大血药浓度(Cmax)和肿瘤内药物浓度(T)分别为：Cmax(ug/ml)和T(ug/g)；MMC ADM 5-FU DDP DWA小鼠体内CBDCA Cmax 1.09 1.44 44.7 4.8 30.3 61.2 Cmax人为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)0.9 354.6 3.1 42.9 30.7 10.4R=0.996有统计学意义(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).