title: Pharmacokinetic profile of Oncofid-S after intraperitoneal and intravenous administration in the rat.
abstract: OBJECTIVE
  Oncofid-S is a bio-conjugate molecule obtained from the binding of campthotecin, SN-38, to hyaluronic acid. In view of a possible clinical development for loco-regional treatment of peritoneal carcinomatosis, this study aimed to establish the pharmacokinetic profile of Oncofid-S after single intraperitoneal or intravenous administration in the rat.
  
  
  METHODS
  Single-dose intraperitoneal or intravenous administrations of Oncofid-S were performed. Groups of six rats were sacrificed at various times (up to 24 and 72 h in i.p. and i.v. study, respectively) after drug injection. Trunk blood, livers and spleens were collected for subsequent analysis. Total SN-38 was assayed by HPLC.
  
  
  RESULTS
  We found that Oncofid-S was poorly absorbed after intraperitoneal injection, the estimated AUC0–72 being less than 2%. The drug was distributed in liver,but not spleen, and was eliminated with a terminal half-life of 16 h. After intravenous dosing, Oncofid-S was found in liver as well as in spleen.
  
  
  CONCLUSIONS
  Here we have demonstrated that Oncofid-S administered intraperitoneally in the rat was poorly absorbed into the systemic circulation, even after the administration of an extremely high dose. This finding reinforces the rationale for developing Oncofid-S in the loco-regional intraperitoneal treatment of peritoneal carcinomatosis in man.
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tringali
authors.forename: Fabio
authors.initials: F
authors.lastname: Bettella
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Greco
authors.forename: Monica
authors.initials: M
authors.lastname: Campisi
authors.forename: Davide
authors.initials: D
authors.lastname: Renier
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C561038:ONCOFID-S; D006820:Hyaluronic Acid; D002166:Camptothecin