title: Pharmacologic effects of cisplatin microspheres on peritoneal carcinomatosis in rodents.
abstract: BACKGROUND
  A new drug-delivery formulation of cisplatin, whereby cisplatin was incorporated in lactic acid oligomer microspheres (CDDP-MS), has been developed in dosage form for peritoneal carcinomatosis and has been designed to release 70% of the incorporated cisplatin slowly during a period of 3 weeks. In this study, its pharmacologic effects were examined in rodents.
  
  
  METHODS
  CDDP-MS was tested to determine (1) tissue distribution of cisplatin after intraperitoneal administration of cisplatin at 3.0 mg/kg body weight to rats, (2) acute toxicity in mice when injected intraperitoneally, and (3) therapeutic effects on peritoneal carcinomatosis induced by transplantable M5076 tumors in mice.
  
  
  RESULTS
  These experiments revealed the following: (1) CDDP-MS resulted in a higher cisplatin concentration in tissues adjacent to the peritoneum for a longer period, and the concentration of cisplatin measured in the rest of the body was lower than that delivered by the cisplatin aqueous solution; (2) the 50% lethal dose value, determined by the Litchfield-Wilcoxon method, was 23.8 mg/kg body weight in CDDP-MS in terms of cisplatin, whereas in the cisplatin aqueous solution it was 13.5 mg/kg body weight; (3) CDDP-MS enhanced therapeutic effects when compared with the same toxicity dosage of cisplatin aqueous solution.
  
  
  CONCLUSIONS
  Intraperitoneal CDDP-MS releases cisplatin into the peritoneal cavity for a long time, and it results in less systemic toxicity and greater therapeutic effects on peritoneal carcinomatosis than does cisplatin aqueous solution.
authors.affiliation: First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hagiwara
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: O
authors.initials: O
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Sasabe
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Sakakura
authors.forename: S
authors.initials: S
authors.lastname: Shoubayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ikada
authors.forename: S H
authors.initials: SH
authors.lastname: Hyon
mesh_terms: D000818:Animals; D002214:Capsules; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D002945:Cisplatin