Surfactants influence the distribution of taxanes in peritoneal dissemination tumor-bearing rats

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 (AUCp,0-24 h and AUCa,0-24 h) of paclitaxel were ∼2- and 6-fold larger than those of docetaxel, respectively. The AUCa,0-24 h,ascite/AUCp,0-24 h ratio of paclitaxel was ∼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.