Intracavitary administration: pharmacokinetic advantages of macromolecular anticancer agents against peritoneal and pleural carcinomatoses.
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.


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.


CONCLUSIONS
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.
Kimura
M
M
Department of Surgery, Health Insurance Hitoyoshi General Hospital, Kumamoto, Japan.
Konno
T
T
Miyamoto
Y
Y
Kojima
Y
Y
Maeda
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001201:Ascites; D002417:Cattle; D002860:Chromium Radioisotopes / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D008299:Maleic Anhydrides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D051379:Mice; D016685:Mitomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010529:Peritoneal Cavity; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D010997:Pleural Neoplasms / Q000188:drug therapy*; D011137:Polystyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012510:Sarcoma 180 / Q000188:drug therapy*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000493:pharmacokinetics; D009353:Zinostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D002860:Chromium Radioisotopes; D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D012710:Serum Albumin, Bovine; D016685:Mitomycin; D004317:Doxorubicin; D009353:Zinostatin