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Novel paclitaxel formulations for oral application: a phase I pharmacokinetic study in patients with solid tumours

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Abstract

Purpose

To explore the pharmacokinetics (PKs) of paclitaxel and two major metabolites after three single oral administrations of a novel drinking solution and two capsule formulations in combination with cyclosporin A (CsA) in patients with advanced cancer. Moreover, the tolerability and safety of the formulations was studied. In addition, single nucleotide polymorphisms in the multidrug resistance (MDR1) gene were determined.

Patients and methods

Ten patients were enrolled and randomized to receive CsA 10 mg/kg followed by oral paclitaxel 180 mg given as (1) drinking solution (formulation 1), (2) capsule formulation 2B, and (3) capsule formulation 2C on day 1, 8, or 15.

Results

The median C max of paclitaxel was 0.42 (0.23–0.96), 0.48 (0.08–0.59), and 0.39 (0.11–1.03) μg/ml and the area under the plasma concentration–time curve was 2.83 (1.69–5.12), 2.01 (1.57–3.04), and 2.67 (1.05–3.61) μg h/ml following administration of formulations 1, 2B, and 2C, respectively. The novel formulations were tolerated after single oral dose without causing relevant gastrointestinal or haematological toxicity.

Conclusions

The PK and metabolism of paclitaxel were comparable between the oral formulations co-administered with CsA.

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Acknowledgments

We thank Ms Ciska Koopman and Ms Carolien Alderden-Los for the assistance in paclitaxel and CsA analysis and Ms Tessa Bosch and Ms Valerie Doodeman for analysis of genetic polymorphisms.

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Authors and Affiliations

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

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

  2. Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066, Amsterdam, The Netherlands

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

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

    H. Rosing, A. D. R. Huitema & J. H. Beijnen

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

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

  5. Ivax Research, Inc., 4400 Biscayne Boulevard, Miami, FL, 33137, USA

    M. R. Fetell

Authors
  1. S. A. Veltkamp
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  2. H. Rosing
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  3. A. D. R. Huitema
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  4. M. R. Fetell
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  5. A. Nol
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  6. J. H. Beijnen
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  7. J. H. M. Schellens
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Correspondence to S. A. Veltkamp.

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Veltkamp, S.A., Rosing, H., Huitema, A.D.R. et al. Novel paclitaxel formulations for oral application: a phase I pharmacokinetic study in patients with solid tumours. Cancer Chemother Pharmacol 60, 635–642 (2007). https://doi.org/10.1007/s00280-006-0405-4

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  • DOI: https://doi.org/10.1007/s00280-006-0405-4

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