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.

Tringali, G., Bettella, F., Greco, M. C., Campisi, M., Renier, D., Navarra, P., Pharmacokinetic profile of Oncofid-S after intraperitoneal and intravenous administration in the rat., <<JOURNAL OF PHARMACY AND PHARMACOLOGY>>, 2012; 2012 (64(3)): 360-365. [doi:10.1111/j.2042-7158.2011.01417.x] [http://hdl.handle.net/10807/7361]

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

Tringali, Giuseppe;Greco, Maria Cristina;Navarra, Pierluigi
2012

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.
2012
Inglese
Tringali, G., Bettella, F., Greco, M. C., Campisi, M., Renier, D., Navarra, P., Pharmacokinetic profile of Oncofid-S after intraperitoneal and intravenous administration in the rat., <<JOURNAL OF PHARMACY AND PHARMACOLOGY>>, 2012; 2012 (64(3)): 360-365. [doi:10.1111/j.2042-7158.2011.01417.x] [http://hdl.handle.net/10807/7361]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/7361
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