The influence of ovarian cancer induced peritoneal carcinomatosis on the pharmacokinetics of albendazole in nude mice.

Angiogenesis in the peritoneal cavity arising from ovarian cancer leads to peritoneal carcinomatosis, malignant ascites formation, morbidity and high mortality. Recent studies in our laboratory have shown albendazole (ABZ) to be a potent inhibitor of angiogenesis and malignant ascites formation. The current study was designed to find the pharmacokinetics of the drug and its major metabolites albendazole sulfoxide (ABZSO) and albendazole sulfone (ABZSO(2)) in an experimental model of ovarian cancer. Additionally, we sought to investigate if the cancer-induced changes in the peritoneal cavity would affect the kinetics of ABZ. On this basis, ABZ was administered 150 mg/kg intraperitoneally to groups of mice bearing peritoneal carcinomatosis and also to groups of healthy mice with no tumor. Blood and peritoneal wash samples were collected for up to 72 h. Concentration of ABZ and its metabolites in the samples were analysed by an established high performance liquid chromatography method. In the healthy mice, drug and metabolite concentrations were found to be low to undetectable. On the contrary, tumor-bearing mice had higher levels of ABZSO in both the plasma and their peritoneal wash. This may at least in part be attributed to the high vascular endothelial growth factor levels present in the peritoneal cavity of the diseased mice. The data obtained in this study suggest that peritoneal carcinomatosis changes ABZ absorption from the peritoneal cavity.