Basic Pharmacokinetics and Pharmacodynamic Principles

  • Chris H. Takimoto
Part of the Cancer Treatment and Research book series (CTAR, volume 106)


The successful development of new molecules with utility in the prevention and treatment of cancer requires a thorough understanding of the pharmacologic properties of these agents. This includes characterizing their interactions with specific molecular targets and defining their pharmacokinetic and pharmacodynamic properties early in the clinical development process. Pharmacokinetics is the analysis of drug absorption, distribution, metabolism, and excretion.1 Often, a drug’s pharmacokinetic profile is summarized by a mathematical representation of its concentration in plasma over time. Understanding a drug’s pharmacokinetic properties is important both for the rational use of these new agents and for explaining the interpatient and intrapatient variability that occurs when these agents are administered to large populations of patients. Pharmacodynamics extends these observations by relating time-dependent kinetic processes to actual clinical drug effects including include both therapeutic and toxic drug actions. Therefore, pharmacodynamics is important because it is ultimately the discipline that relates drug pharmacokinetics to clinically relevant endpoints.


Central Compartment Mean Residence Time Elimination Rate Constant Chemoprevention Agent Drug Elimination 
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  1. 1.
    Gilbaldi M. Introduction to Pharmacokinetics.In:Gilbaldi M, ed.Biopharmaceutics and Clinical Pharmacokinetics4th Edition ed. Philadelphia:Lea &Febiger; 1991:113.Google Scholar
  2. 2.
    Takimoto CH, Lu ZL, Shang R, Liang MD, Larson LV, Cantilena LR, Grem JL, Allegra CJ, Diasio RB, Chu E. Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency.Clin Cancer Res.1996;2:477–481.PubMedGoogle Scholar
  3. 3.
    Chabner BA, Stoller RG, Hande K, Jacobs S, Young RC. Methotrexate disposition in humans: case studies in ovarian cancer and following high-dose infusion.Drug Metab Rev.1978;8:107–17.CrossRefGoogle Scholar
  4. 4.
    Ratain MJ. Therapeutic relevance of pharmacokinetics and pharmacodynamics.Sem Oncol.1992;19:8–13.Google Scholar
  5. 5.
    Grem JL, Yee LK, Venzon DJ, Takimoto CH, Allegra CJ. Inter-and intraindividual variation in dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells.Cancer Chemother Pharmacol.1997;40:117–25.PubMedCrossRefGoogle Scholar
  6. 6.
    Greenblatt DJ, Koch-Weser J. Clinical pharmacokinetics.N Engl J Med.1975;293:702–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Greenblatt DJ, Koch-Weser J. Clinical pharmacokinetics (second of two parts).N Engl J Med.1975;293:964–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Bourne DWA, Triggs EG, Eadie MJ.Pharmacokinetics for the non-mathematical.Lancaster: MTP Press Limited; 1986.Google Scholar
  9. 9.
    Theodore WH. Basic principles of clinical pharmacology.Clin Neuropharmacol.1990;8:1–13.Google Scholar
  10. 10.
    Collins JM. Pharmacokinetics and clinical monitoring. In: Chabner BA, Longo DL, eds.Cancer chemotherapy and biotherapy: Principles and practice.Second edition ed. Philadelphia: Lippincott-Raven; 1996.Google Scholar
  11. 11.
    Winter ME. Digoxin. In: Winter ME, ed.Basic clinical pharmacokinetics.Third edition ed. Vancouver: Applied Therapeutics, Inc.; 1994:198–235.Google Scholar
  12. 12.
    Bourne DWA.Mathematical modeling of pharmacokinetic data.Lancaster:Technomic Publishing Co.; 1995.Google Scholar
  13. 13.
    Gabrielsson J, Weiner D.Pharmacokinetic and pharmacodynamic data analysis concepts and applications.Second edition ed. Stockholm: Swedish Pharmaceutical Press; 1997.Google Scholar
  14. 14.
    Noe DA. Noncompartmental pharmacokinetic analysis. In: Grochow LB, Ames MM, eds.A clinician’s guide to chemotherapy: Pharmacokinetics and pharmacodynamics.Baltimore: Williams & Wilkins; 1998:515–530.Google Scholar
  15. 15.
    Sambol NC, Sechaud R. The population approach: Description and applications to anticancer agents. In: Grochow LB, Ames MM, eds.A clinician’s guide to chemotherapy: Pharmacokinetics and pharmacodynamics.Baltimore:Williams &Wilkins; 1998:531–549.Google Scholar
  16. 16.
    Ratain MJ, Schilsky RL, Conley BA, Egorin MJ. Pharmacodynamics in cancer therapy.J Clin Oncol.1990;8:1739–1753.PubMedGoogle Scholar

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© Springer Science+Business Media New York 2001

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  • Chris H. Takimoto

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