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Conditioning Regimens

The pharmacokinetics and safety of twice daily i.v. BU during conditioning in pediatric allo-SCT recipients

Bone Marrow Transplantation volume 48, pages 19–25 (2013)Cite this article

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Abstract

Intravenous BU divided four times daily (q6 h) has been shown to be safe and effective in pediatric allo-SCT recipients. Though less frequent dosing is desirable, pharmacokinetic (PK) data on twice daily (q12 h) i.v. BU administration in pediatric allo-SCT recipients is limited. We prospectively examined the PK results in a cohort of pediatric allo-SCT recipients receiving i.v. BU q12 h as part of conditioning before allo-SCT. BU levels were obtained after the first dose of conditioning. PK parameter analysis (n=49) yielded the following 95% confidence intervals (CI95): weight-normalized volume of distribution: 0.65–0.73 L/kg; t1/2: 122–147 min; weight-normalized clearance (CLn): 3.4–4.3 mL/min/kg; and area under the curve: 1835–2180 mmol × min/L. From these results, a steady state concentration was calculated with CI95 between 628–746 ng/mL. Comparison between recipients ⩽4 vs >4 years old revealed significant differences in t1/2 (mean: 115 vs 146 min, P=0.008) and CLn (mean: 4.4 vs 3.5 mL/min/kg, P=0.038). Intravenous BU q12 h had a comparable PK to i.v. BU q6 h PK seen in the literature, and in pediatric allo-SCT recipients, is a feasible, attractive alternative to i.v. q6h dosing.

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Acknowledgements

We would like to thank the patients and families that participated in these studies and the laboratory staff at the clinical toxicology laboratory at HUP.

This work was supported in part by grants from the Pediatric Cancer Research Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21 AR49330; MSC), Marisa Fund, Sonia Scaramella Fund, Paul Luisi Foundation, Brittany Barron Fund and the Doris Duke Charitable Foundation.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Columbia University, New York, NY, USA

    J B Le Gall, O Militano, M Bhatia, P Satwani, D George & J H Garvin

  2. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    M C Milone & L M Shaw

  3. Bristol-Myers Squibb, Princeton, NJ, USA

    I M Waxman & M B Bradley

  4. Department of Pediatrics, New York Medical College, Valhalla, NY, USA

    L Harrison, D Duffy, C van de Ven, E Morris & M S Cairo

  5. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    M B Geyer

  6. Department of Pathology and Cell Biology, Columbia University, New York, NY, USA

    J Schwartz

  7. Department of Surgery, University of California, San Francisco, CA, USA

    L A Baxter-Lowe

  8. Department of Medicine, New York Medical College, Valhalla, NY, USA

    M S Cairo

  9. Department of Pathology, New York Medical College, Valhalla, NY, USA

    M S Cairo

  10. Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA

    M S Cairo

  11. Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA

    M S Cairo

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  1. J B Le Gall
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  2. M C Milone
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  3. I M Waxman
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  6. D Duffy
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  7. C van de Ven
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  10. E Morris
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  13. D George
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  14. J H Garvin
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  16. J Schwartz
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Correspondence to M S Cairo.

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Competing interests

IMW and MBB currently work for Bristol Myers Squibb. All other authors declare no conflict of interest.

Additional information

Presented in part at the American Society of Blood and Marrow Transplantation (ASBMT), February, 2011, Honolulu, Hawaii

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Le Gall, J., Milone, M., Waxman, I. et al. The pharmacokinetics and safety of twice daily i.v. BU during conditioning in pediatric allo-SCT recipients. Bone Marrow Transplant 48, 19–25 (2013). https://doi.org/10.1038/bmt.2012.105

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  • DOI: https://doi.org/10.1038/bmt.2012.105

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