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Intracavitary administration: pharmacokinetic advantages of macromolecular anticancer agents against peritoneal and
M Kimura1, T Konno, Y Miyamoto
1Department of Surgery, Health Insurance Hitoyoshi General Hospital, Kumamoto, Japan.
Background:
Pleural and peritoneal carcinomatoses are quite difficult to control in patients with advanced cancer. We have devised a suitable formulation of anticancer agents to be injected by the intracavitary route.
Materials And Methods:
The pharmacokinetics of macromolecular anticancer agent, copoly(styrene/maleic acid)-conjugated neocarzinostatin (smancs) and radiolabeled albumin were studied after intraperitoneal administration to ascitic tumor-bearing rats and mice, and were compared with the pharmacokinetics of other low-molecular-weight anticancer agents, mitomycin C (MMC) and doxorubicin (DOX).
Results:
Pharmacokinetic analyses indicated that smancs showed a much higher drug concentration for a longer time in the peritoneal cavity, and a much lower drug concentration in the blood circulation than did MMC or DOX. The cavity/blood ratios of the area under the concentration curve (AUC), of smancs, bovine serum albumin (BSA), DOX, and MMC were 9.69, 7.06, 1.38, 1.15, respectively.
Conclusion:
These results suggest that macromolecular agents are cleared more slowly from the cavitary compartment and remain there at a high concentration while the blood concentration remains low.