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Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients

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Abstract

Purpose

There is significant inter-patient variability in the pharmacokinetics of pegylated liposomal doxorubicin (PLD). Identification of factors affecting the pharmacokinetics of PLD would enable personalization of therapy. We previously reported that age, gender, body composition, and monocytes affect the clearance of other liposomal agents. Therefore, we evaluated how these factors affect the pharmacokinetics of PLD.

Methods

Pharmacokinetic studies of PLD were performed as part of phase I and II studies in 70 patients with solid tumors or Kaposi’s sarcoma. The effects of monocyte count, age, gender, and body composition on PLD clearance were examined.

Results

There was a 15.3-fold variability in PLD clearance. Body surface area-based dosing did not significantly reduce the variability in PLD clearance. The mean ± SD clearance for patients <60 years old and ≥60 years old were 54.6 ± 28.5 and 23.3 ± 10.8 mL/h/m2, respectively (P < 0.0001), and for female and male patients were 23.7 ± 18.8 and 55.6 ± 26.8 mL/h/m2, respectively (P < 0.0001). A reduction in pre-cycle monocyte count was associated with a greater reduction in PLD clearance.

Conclusions

Age, gender, and monocyte counts appear to correlate with PLD clearance. Further investigation of the association between these factors, PLD pharmacokinetics, and clinical outcomes (efficacy and toxicity) is warranted. These effects on the pharmacokinetics of PLD may be an approach for personalizing PLD therapy and may affect other pegylated liposomes and nanoparticle agents.

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Conflicts of interest

William C. Zamboni received minor compensation (<$10,000) as a consultant for Johnson & Johnson. All other authors declare that they have no conflicts of interest.

Author information

Author notes

  1. Ninh M. La-Beck

    Present address: Center for Immunotherapeutic Research and Department of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center, 1718 Pine St, Abilene, TX, 79601, USA

Authors and Affiliations

  1. UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Ninh M. La-Beck & William C. Zamboni

  2. Department of Mathematics, Carlow University, Pittsburgh, PA, 15213, USA

    Beth A. Zamboni

  3. Department of Oncology, Shaare Zedek Medical Center and Hebrew University-School of Medicine, POB 3235, 91031, Jerusalem, Israel

    Alberto Gabizon & Hilary Schmeeda

  4. Department of Clinical Pharmacology, Pfizer, Inc., 10578 Science Center Drive, CB 10, San Diego, CA, 92121, USA

    Michael Amantea

  5. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Paola A. Gehrig

  6. Molecular Therapeutics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    William C. Zamboni

  7. Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    William C. Zamboni

  8. Carolina Center of Cancer Nanotechnology Excellence, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    William C. Zamboni

  9. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 120 Mason Farm Road, suite 1013, CB 7361, Chapel Hill, NC, 27599-7361, USA

    William C. Zamboni

Authors
  1. Ninh M. La-Beck
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  2. Beth A. Zamboni
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  3. Alberto Gabizon
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  4. Hilary Schmeeda
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  5. Michael Amantea
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  7. William C. Zamboni
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Correspondence to William C. Zamboni.

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La-Beck, N.M., Zamboni, B.A., Gabizon, A. et al. Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients. Cancer Chemother Pharmacol 69, 43–50 (2012). https://doi.org/10.1007/s00280-011-1664-2

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  • DOI: https://doi.org/10.1007/s00280-011-1664-2

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