In vivo toxicity and bioavailability of Taxol and a paclitaxel/beta-cyclodextrin formulation in a rat model during HIPEC.
Ann Surg Oncol
; 17(9): 2510-7, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-20339948
BACKGROUND: Peritoneal carcinomatosis (PC) remains a dreaded clinical syndrome and a common evolution of gastrointestinal and ovarian cancers. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has emerged as a promising strategy in the management of PC. In this study, a novel paclitaxel (Pac) formulation was investigated for its toxicity and bioavailability during HIPEC compared with Taxol. MATERIALS AND METHODS: The maximum tolerated dose (MTD) after HIPEC of both formulations (Taxol and Pac/RAME-beta-CD) was determined. MTD was defined as the highest nonlethal dose with a reduction in body weight of < or = 10% over 2 weeks. Blood parameters (red blood cell and white blood cell count, creatinine, ALT, and GGT) were evaluated over 20 days. Bioavailability of both Pac formulations after HIPEC was determined under normothermic (37 degrees C) and hyperthermic (41 degrees C) conditions for 90 min. RESULTS: Following HIPEC, both formulations had a similar MTD: 0.24 mg paclitaxel per ml. Red blood cell count decreased to a minimum after 10 days and was not fully recovered after 20 days for both formulations. White blood cell monitoring showed a significant increase in neutrocytes at day 10 and 15 for the Pac/RAME-beta-CD formulation. Liver and kidney parameters did not change significantly. Bioavailability data of Pac/RAME-beta-CD showed a 40-fold increase of the area under the curve (AUC) of plasma concentrations compared with Taxol. Hyperthermia yielded no significant differences in bioavailability data. CONCLUSION: These results showed that both formulations had a similar toxicity profile but differed significantly in bioavailability.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peritoneo
/
Carcinógenos
/
Paclitaxel
/
Beta-Ciclodextrinas
/
Hipertermia Inducida
/
Antineoplásicos Fitogénicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Ann Surg Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2010
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
Estados Unidos