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 (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.
Kamijo
Yukio
Y
Department of Medicinal Informatics, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Ito
Chie
C
Nomura
Masaaki
M
Sai
Yoshimichi
Y
Miyamoto
Ken-ichi
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001201:Ascites / Q000378:metabolism; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008113:Liver Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D011136:Polysorbates / Q000494:pharmacology*; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology*; D043823:Taxoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D011136:Polysorbates; D013501:Surface-Active Agents; D043823:Taxoids; D000077143:Docetaxel; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol