PLASMA AND TISSUE DISPOSITION OF PACLITAXEL (TAXOL) AFTER INTRAPERITONEAL ADMINISTRATION IN MICE

The pharmacokinetics of single intraperitoneal doses of paclitaxel (18 and 36 mg/kg) in mice were investigated in the present study. The ana lysis of drug concentrations by HPLC indicated that the plasma C-max ( 13.0 +/- 3.1 and 25.7 +/- 2.8 mu g/ml, respectively) were reached at t he 2nd hr. The values of CL were low (0.06 and 0.1 ml/min, respectivel y), and t1/2 beta values of 3.0 and 3.7 hr were found, after 18 and 36 mg/kg, respectively. The highest tissue concentrations were observed in the liver (50.2 +/- 3.1 and 92.0 +/- 9.5 mu g/g, respectively), fol lowed by the pancreas (39.3 +/- 9.9 mu g/g) and the ovary (53.4 +/- 5. 6 mu g/g) after 18 and 36 mg/kg, respectively. In the case of the coli c tissue, paclitaxel C-max were 14.4 +/- 0.8 and 32.8 +/- 3.5 mu g/g a t the 3rd hr, respectively, with sustained drug levels still detectabl e 24 hr after treatment. Paclitaxel C-max values of 12.7 +/- 3.0 and 5 3.4 +/- 5.6 mu g/g were detected in the ovary after 18 and 36 mg/kg, r espectively. The overall results provide evidence that, after intraper itoneal administration, paclitaxel concentrates in peritoneal organs; however, the intraperitoneal route does not prevent systemic drug expo sure, allowing high and sustained levels of paclitaxel also in several extraperitoneal tissues.