Skip to main content

Abstract

Pharmacokinetic variability in pediatric patients due to maturational changes in organ function, effects of concomitant disease, and drug toxicity or interactions commonly results in drug clearances that differ by a factor of 4 or 5. This intersubject pharmacokinetic variability has been shown to correlate to an increased likelihood of toxicity in patients with low drug clearances, and therapeutic failure in patients with high drug clearances [1, 2]. Pharmacokinetic and pharmacodynamic modeling strategies have been developed and incorporated into clinical studies intended to define the unique pharmacokinetics of anticancer drugs in pediatric patients, identify clinical correlates (e. g., patient characteristics, laboratory indices of organ function) of pharmacokinetic differences, and adjust dosage regimens to control for pharmacokinetic variability.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. W. E. Evans, W. R. Crom, M. Abromowitch, et al. Clinical pharmacodynamics of high dose methotrexate in acute lymphocytic leukemia. N. Engl. J. Med. 314:471–477 (1986).

    Article  PubMed  CAS  Google Scholar 

  2. J. H. Rodman, M. Abromowitch, J. A. Sinkule et al. Clinical Pharmacodynamics of Continuous Infusion Teniposide: Systemic Exposure as a Determinant of Response in a Phase I trial. J. Clin. Oncol. 7:1007–1014 (1987).

    Google Scholar 

  3. J. H. Rodman, M. Sunderland, R. L. Kavanagh, J. Ochs, J. Yalowich, W. E. Evans, and G. K. Rivera. Pharmacokinetics of continuous infusion methotrexate and teniposide in pediatric cancer patients. Cancer Res. 50:4267–4271 (1990).

    PubMed  CAS  Google Scholar 

  4. R. S. Day. Treatment sequencing, asymmetry, and uncertainty: protocol strategies for combination chemotherapy. Cancer Res. 46:3876–3885 (1986).

    PubMed  CAS  Google Scholar 

  5. A. J. Coldman, C. M. L. Coppin, and J. H. Goldie. Models for Dose Intensity. Math. Biosci. 92:97–113 (1988).

    Article  Google Scholar 

  6. C. C. Peck and J. H. Rodman. Analysis of clinical pharmacokinetic data for individualizing drug dosage regimen. In W. E. Evans, J. J. Schentag, and W. J. Jusko (eds.), Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring, Applied Therapeutics, Inc., Spokane, 1986, pp. 55–82.

    Google Scholar 

  7. D. Z. D’Argenio and A. Schumitzky. A program package for simulation and parameter estimation in pharmacokinetic systems. Comp. Prog. Biomed. 9:115–134 (1979).

    Article  Google Scholar 

  8. S. L. Beal. Population pharmacokinetic data and parameter estimation based on their first two statistical moments. Drug Metab. Rev. 15:173–194 (1984).

    Article  PubMed  CAS  Google Scholar 

  9. S. L. Beal and L. B. Sheiner. NONMEM User’s Guides, NONMEM Project, University of California, San Francisco, 1989.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media New York

About this chapter

Cite this chapter

Rodman, J.H., Evans, W.E. (1991). Targeted Systemic Exposure for Pediatric Cancer Therapy. In: D’Argenio, D.Z. (eds) Advanced Methods of Pharmacokinetic and Pharmacodynamic Systems Analysis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9021-4_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9021-4_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9023-8

  • Online ISBN: 978-1-4757-9021-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics