Department of Medicinal Informatics, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Cancer Lett. 2010 Jan 28;287(2):182-6. doi: 10.1016/j.canlet.2009.06.018. Epub 2009 Jul 15.
The effects of surfactants on the disposition kinetics of docetaxel and paclitaxel were examined in tumor-bearing rats. Taxol and Taxotere were administered intraperitoneally to AH130 tumor-bearing rats. Plasma and ascitic AUCs (AUC(p,0-24h) and AUC(a,0-24h)) of paclitaxel were approximately 2- and 6-fold larger than those of docetaxel, respectively. The AUC(a,0-24h,ascite)/AUC(p,0-24h) ratio of paclitaxel was approximately 3-fold larger than that of docetaxel. The first-order peritoneal cavity-systemic circulation absorption rate constant of paclitaxel was 1/8 that of docetaxel. Docetaxel concentrations in free and solid tumors in the peritoneal cavity were higher than those of paclitaxel. The in vitro uptake of paclitaxel by AH130 cells was inhibited by Cremophor EL and Polysorbate-80. Docetaxel uptake was only slightly affected by these surfactants. These results indicated that Taxol scarcely released paclitaxel, while Taxotere easily released docetaxel, enabling its distribution to tumors disseminated in the peritoneal cavity.
在荷瘤大鼠中研究了表面活性剂对多西紫杉醇和紫杉醇处置动力学的影响。将紫杉醇和多西紫杉醇腹腔内给予 AH130 荷瘤大鼠。紫杉醇的血浆和腹水 AUC（AUC(p,0-24h) 和 AUC(a,0-24h)）分别约为多西紫杉醇的 2 倍和 6 倍。紫杉醇的 AUC(a,0-24h,ascite)/AUC(p,0-24h) 比值约为多西紫杉醇的 3 倍。紫杉醇的第一阶腹膜腔-全身循环吸收速率常数为多西紫杉醇的 1/8。多西紫杉醇在腹腔游离和实体肿瘤中的浓度高于紫杉醇。紫杉醇在 AH130 细胞中的体外摄取被 Cremophor EL 和聚山梨酯 80 抑制。这些表面活性剂对多西紫杉醇的摄取仅有轻微影响。这些结果表明，Taxol 几乎不释放紫杉醇，而 Taxotere 容易释放多西紫杉醇，使其分布到腹腔内播散的肿瘤中。
