[Study for modifying activity of solvents on antitumor activity of paclitaxel].
Paclitaxel, a novel diterpenoid compound, has been used by dissolving in Cremophor EL (polyoxyethylene castor oil) due to its poor aqueous solubility. Cremophor EL was shown to reverse multidrug resistant phenotypes of various cell lines as well as to reverse cross-resistance to paclitaxel of a multidrug resistant cell line in vitro. Thus, a study was carried out to determine the modifying activity of Cremophor EL on the antitumor activity of paclitaxel against P388 leukemia, adriamycin-resistant subline (P388/ADM) and vincristine-resistant subline (P388/VCR) in vivo. Dimethyl sulfoxide (DMSO) was used as a counterpart solvent. The results showed that, although no significant antitumor activity was observed by paclitaxel in both solvents against P388/ADM, a significantly higher antitumor activity was induced by paclitaxel dissolved in Cremophor EL-based solvent compared with DMSO-based solvent against P388/VCR. However, more significant difference in the antitumor activity of paclitaxel against P388 parental line was observed between two solvents and both resistant sublines showed an obvious cross-resistance to paclitaxel. Therefore, it appeared that cross-resistance reversing activity of Cremophor EL is not so high as to be detectable at in vivo level.
Fujimoto
S
S
Division of Chemotherapy, Chiba Cancer Center Research Institute.
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology*; D012997:Solvents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
D012997:Solvents; D014750:Vincristine; C000515:cremophor EL; D004317:Doxorubicin; D017239:Paclitaxel; D005990:Glycerol; D004121:Dimethyl Sulfoxide