Publication
Title
In vivo toxicity and bioavailability of Taxol® and a paclitaxel/-cyclodextrin formulation in a rat model during HIPEC
Author
Abstract
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-β-CD) was determined. MTD was defined as the highest nonlethal dose with a reduction in body weight of ≤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°C) and hyperthermic (41°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-β-CD formulation. Liver and kidney parameters did not change significantly. Bioavailability data of Pac/RAME-β-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.
Language
English
Source (journal)
Annals of surgical oncology. - Philadelphia, Pa
Publication
Philadelphia, Pa : 2010
ISSN
1068-9265
Volume/pages
17:9(2010), p. 2510-2517
ISI
000281858600034
Full text (Publishers DOI)
Full text (publishers version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 23.04.2015
Last edited 10.05.2017