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

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium

    W. Bouquet PhD, E. Adriaens PhD, A. Almeida Pharm, T. Quinten Pharm, J. P. Remon PhD & C. Vervaet PhD

  2. Department of Abdominal Surgery, Ghent University Hospital, Ghent, Belgium

    W. Ceelen PhD & P. Pattyn PhD

  3. Laboratory of Radiopharmacy, Ghent University, Ghent, Belgium

    F. De Vos PhD

  4. Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium

    M. Peeters PhD

Authors
  1. W. Bouquet PhD
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  2. W. Ceelen PhD
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  3. E. Adriaens PhD
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  4. A. Almeida Pharm
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  5. T. Quinten Pharm
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  6. F. De Vos PhD
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  9. J. P. Remon PhD
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  10. C. Vervaet PhD
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Corresponding author

Correspondence to C. Vervaet PhD.

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Bouquet, W., Ceelen, W., Adriaens, E. et al. In vivo Toxicity and Bioavailability of Taxol® and a Paclitaxel/β-Cyclodextrin Formulation in a Rat Model During HIPEC. Ann Surg Oncol 17, 2510–2517 (2010). https://doi.org/10.1245/s10434-010-1028-x

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  • DOI: https://doi.org/10.1245/s10434-010-1028-x

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