In vivo Toxicity and Bioavailability of Taxol® and a Paclitaxel/β-Cyclodextrin Formulation in a Rat Model During HIPEC

Abstract

These results showed that both formulations had a similar toxicity profile but differed significantly in bioavailability.

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

“…Based on the maximum tolerated dose of Taxol ® (0.24 mg/ml) determined by Bouquet et al in Wag/Rij rats (15), and based on the lower body weight and the reduced immune system of the athymic nude rats used in this study, a PTX dose of 0.21 mg/ml was used as starting point. To determine MTD, the PTX concentration in the formulation was gradually increased (increments of 0.03 mg/ml) using 1 rat per concentration.…”

Rationale for Integrated Procedures: Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined

“…Their cell-cycle-specific mechanism of action makes them a particularly good candidate for repeat application; for example, in EPIC, NIPS, or normothermic adjuvant postoperative IP-CHT [45,61,62]. Research efforts now focus on developing novel taxane formulations to increase bioavailability [100].…”

Antitumour Efficacy of Two Paclitaxel Formulations for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in an In Vivo Rat Model

“…An incision was made in the abdomen and in-and outlet tubings (Marprene® and Pumpsil® (Watson-Marlow, Zwijnaarde, Belgium) for Pac/RAME-β-CD and Taxol® administration, respectively) were placed in the peritoneal cavity for perfusion with the cytostatic solution, containing 0.24 mg/ml paclitaxel (= 0.28 mM) for both formulations, during 45 min. The administered dose is the maximum tolerated dose previously determined during HIPEC treatment with Pac/RAME-β-CD and Taxol® (11). A roller pump (Watson-Marlow®, Zwijnaarde, Belgium) circulated the perfusate at a flow rate of 30 ml/min through a heat exchanger, ensuring a temperature of 37°C (normothermic condition) or 41°C (hyperthermic condition, selected based on literature data) (4,11,12).…”