Pharmacokinetic profile of Oncofid-S after intraperitoneal and intravenous administration in the rat.

Giuseppe Tringali, Pierluigi Navarra, Maria Cristina Greco, F Bettella, M Campisi, D Renier

Risultato della ricerca: Contributo in rivistaArticolo in rivista

11 Citazioni (Scopus)

Abstract

OBJECTIVES: 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. KEY FINDINGS: 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.
Lingua originaleEnglish
pagine (da-a)360-365
Numero di pagine6
RivistaJOURNAL OF PHARMACY AND PHARMACOLOGY
Volume2012
Stato di pubblicazionePubblicato - 2012

Keywords

  • Hyaluronic acid
  • Intraperitoneal route
  • Intravenous route
  • Rat
  • SN-38

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