Pharmacokinetic evaluation of intraperitoneal doxorubicin in rats.

ABSTRACT

The intraperitoneal (ip) administration of doxorubicin (DOX) is considered to be an important approach for the treatment of peritoneal tumors, because the prognosis of peritoneal cancer is generally poor due to its refractoriness to conventional chemotherapy. In the present study, we examined the disposition behavior of DOX after ip administration in rats to evaluate the adequacy of the ip administration of DOX on the basis of pharmacokinetic aspects. By comparing the area under the serum concentration-time curve (AUC) after ip and intravenous (iv) dosing of 5 mg/kg DOX, the bioavailability of intraperitoneally administered DOX was estimated as 43.8%. This finding suggests that the majority of DOX remained in the abdominal cavity without being incorporated into the systemic circulation. The mean residence time (MRT) of DOX after its ip administration was about 80% longer than that after its iv administration, which indicated the slow absorption process associated with ip application. No significant difference was observed in the elimination rates of systemically absorbed DOX. These results indicate that the ip administration of DOX likely provided an adequate opportunity for it to interact with peritoneal tumors by maintaining sufficient DOX levels while reducing its systemic exposure