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A pharmacokinetic and safety study of a novel polymeric paclitaxel formulation for oral application

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Abstract

Purpose: To investigate the pharmacokinetics, safety, and tolerability of a new oral formulation of paclitaxel containing the polymer polyvinyl acetate phthalate in patients with advanced solid tumors. Patients and methods: A total of six patients received oral paclitaxel as single agent given as a single dose of 100 mg on day 1, oral paclitaxel 100 mg in combination with cyclosporin A (CsA) 10 mg/kg both given as a single dose on day 8, and i.v. paclitaxel (Taxol®) 100 mg as a 3-h infusion on day 15. Results: The AUC (mean ± standard deviation) values of paclitaxel after oral administration without CsA and with CsA were 476 ± 254 and 967 ± 779 ng/ml h, respectively. T max was 4.0 ± 0.9 h after oral paclitaxel without CsA, and 6.0 ± 3.1 h after oral paclitaxel with CsA. The mean AUC after oral administration as single agent was 13% of the AUC after i.v. administration of paclitaxel, and increased to 26% after co-administration with CsA. No haematological toxicities were observed, and only mild (CTC-grade 1 and 2) non-hematological toxicities occurred after oral intake of paclitaxel with or without CsA. Conclusion: The AUC of the new polymeric paclitaxel formulation increased a factor 2 in combination with CsA, which confirms that CsA co-administration can also improve exposure to paclitaxel after oral administration of a polymeric formulation. Because of the delayed release of paclitaxel from this formulation, we hypothesize that a split-dose regimen of CsA where it is administered before and after paclitaxel administration will further increase the systemic exposure to paclitaxel up to therapeutic levels. The formulation was well tolerated at the dose of 100 mg without induction of severe toxicities.

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Authors and Affiliations

  1. Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    S. A. Veltkamp & J. H. M. Schellens

  2. Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam, The Netherlands

    S. A. Veltkamp, J. H. Beijnen & J. H. M. Schellens

  3. Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, 1066 EC, Amsterdam, The Netherlands

    C. Alderden-Los, H. Rosing & J. H. Beijnen

  4. Division of Biomedical Analysis, Faculty of Pharmaceutical Sciences, University of Utrecht, 3584 CG, Utrecht, The Netherlands

    J. H. Beijnen & J. H. M. Schellens

  5. Apotex Research Inc., Innovative Drug Development, 200 Barmac Drive, Toronto, ON, Canada

    A. Sharma

Authors
  1. S. A. Veltkamp
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  2. C. Alderden-Los
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  3. A. Sharma
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  4. H. Rosing
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  5. J. H. Beijnen
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  6. J. H. M. Schellens
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Correspondence to S. A. Veltkamp.

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Veltkamp, S.A., Alderden-Los, C., Sharma, A. et al. A pharmacokinetic and safety study of a novel polymeric paclitaxel formulation for oral application. Cancer Chemother Pharmacol 59, 43–50 (2007). https://doi.org/10.1007/s00280-006-0245-2

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  • DOI: https://doi.org/10.1007/s00280-006-0245-2

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