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Pharmacokinetics of Commonly used Anti-Leukemic agents in Children

  • Chapter
Childhood Leukemia: Present Problems and Future Prospects

Part of the book series: Developments in Oncology ((DION,volume 65))

Abstract

To treat children with acute lymphoblastic leukemia, the pediatric oncologist must have a basic understanding and appreciation of the clinical pharmacology of vincristine, methotrexate, 6-mercaptopurine, cytarabine (cytosine arabinoside), and corticosteroids. The treating physician should be cognizant of the inter- and intrapatient variabilities in the pharmacokinetics and clinical effects of each of the drugs. The pharmacokinetics of other cancer chemotherapy agents used in the treatment of childhood leukemia should also be known (doxorubicin, asparaginase, teniposide, and cyclophosphamide), but these agents are less commonly used or administered for a short period of the total treatment. Recent laboratory studies and clinical observations have suggested ways in which the agents could be administered more optimally. For the antimetabolites, these include limited bioavailability and the absence of a diurnal variation in oral methotrexate and 6-mercaptopurine, new antifolates with better pharmacological characteristics for oral administration, intravenous therapy with 6-mercaptopurine, and subcutaneous therapy with methotrexate. For corticosteroid therapy, dexamethasone appears to have an advantage over prednisone and prednisolone in treating leukemic cells in the central nervous system. Intrathecal chemotherapy for the prevention of meningeal leukemia is more effective if the dosage is based on the volume of the central nervous system instead of the body surface area. Exposure of systemic tissue to cytotoxic drug concentrations after intrathecal chemotherapy is substantial with methotrexate and negligible with cytarabine.

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Author information

Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, Children’s Hospital and Medical Center, University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, Washington, 98105, USA

    W. Archie Bleyer M.D.

  2. Leukemia Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA

    David G. Poplack M.D. & Frank M. Balis M.D.

  3. Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA

    David G. Poplack M.D.

Authors
  1. W. Archie Bleyer M.D.
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  2. David G. Poplack M.D.
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  3. Frank M. Balis M.D.
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Editor information

Editors and Affiliations

  1. National Children’s Hospital, 3-35-31 Taishido, Setagaya-ku, Tokyo 154, Japan

    Noboru Kobayashi

  2. The National Children’s Hospital Medical Research Center, Tokyo, Japan

    Tai Akera

  3. Department of Virology, The National Children’s Medical Research Center, 3-35-31 Taishido, Setagaya-ku, Tokyo 154, Japan

    Shuki Mizutani

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© 1991 Springer Science+Business Media New York

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Bleyer, W.A., Poplack, D.G., Balis, F.M. (1991). Pharmacokinetics of Commonly used Anti-Leukemic agents in Children. In: Kobayashi, N., Akera, T., Mizutani, S. (eds) Childhood Leukemia: Present Problems and Future Prospects. Developments in Oncology, vol 65. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3898-1_15

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  • DOI: https://doi.org/10.1007/978-1-4615-3898-1_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6739-0

  • Online ISBN: 978-1-4615-3898-1

  • eBook Packages: Springer Book Archive

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