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

Anticancer Res. Jul-Aug 1998;18(4A):2547-50.

Abstract

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Ascites
  • Cattle
  • Chromium Radioisotopes / pharmacokinetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Injections, Intraperitoneal
  • Liver Neoplasms, Experimental / drug therapy*
  • Male
  • Maleic Anhydrides / administration & dosage
  • Maleic Anhydrides / pharmacokinetics*
  • Maleic Anhydrides / therapeutic use
  • Metabolic Clearance Rate
  • Mice
  • Mitomycin / administration & dosage
  • Mitomycin / pharmacokinetics
  • Mitomycin / therapeutic use
  • Peritoneal Cavity
  • Peritoneal Neoplasms / drug therapy*
  • Pleural Neoplasms / drug therapy*
  • Polystyrenes / administration & dosage
  • Polystyrenes / pharmacokinetics*
  • Polystyrenes / therapeutic use
  • Rats
  • Rats, Inbred Strains
  • Sarcoma 180 / drug therapy*
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / pharmacokinetics
  • Zinostatin / administration & dosage
  • Zinostatin / analogs & derivatives*
  • Zinostatin / pharmacokinetics
  • Zinostatin / therapeutic use

Substances

  • Antineoplastic Agents
  • Chromium Radioisotopes
  • Maleic Anhydrides
  • Polystyrenes
  • poly(maleic acid-styrene)neocarzinostatin
  • Serum Albumin, Bovine
  • Mitomycin
  • Doxorubicin
  • Zinostatin