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Use of Toxicokinetic Principles in Drug Development: Bridging Preclinical and Clinical Studies

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Integration of Pharmacokinetics, Pharmacodynamics, and Toxicokinetics in Rational Drug Development

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Abstract

Toxicokinetics has gained wide acceptance in validating dose related drug exposure in safety evaluation studies. Although exposure is confirmed by measuring blood levels, the concept of comparing safe/toxic blood concentrations in animals to those in man has not been fully realized. Furthermore, in many cases, the frequency of dosing in animal safety studies may not match with that proposed for use in man. Many examples exist demonstrating that the efficacy, safety and toxicity of a drug are influenced by the mode and frequency of drug administration. Although physiological differences between various animal species and man make direct extrapolations to man difficult, new techniques have been proposed which may allow for reasonably good estimates of pharmacokinetic parameters in man. A successful extrapolation would be very useful in planning and expediting early clinical trials. The relationship between safe dosages, pharmacologic-toxicologic activities, and blood levels can guide in selecting early dosages for initial administration to man and in subsequent dosing escalation strategy.

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Authors and Affiliations

  1. Medical Research Division, American Cyanamid Company, Pearl River, N.Y., 10965, USA

    Mauricio Leal, Avraham Yacobi & Vijay K. Batra

Authors
  1. Mauricio Leal
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  2. Avraham Yacobi
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  3. Vijay K. Batra
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Editor information

Editors and Affiliations

  1. Pharmacodynamics Research, American Cyanamid Company, Medical Research, Pearl River, New York, USA

    Avraham Yacobi Ph.D. (Director) (Director)

  2. Office of Research Resources, Center for Drug Evaluation and Research, Food and Drug Administration, Washington, D.C., USA

    Jerome P. Skelly Ph.D. (Deputy Director) (Deputy Director)

  3. Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA

    Vinod P. Shah Ph.D. (Acting Deputy Associate Director for Science) (Acting Deputy Associate Director for Science)

  4. Department of Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, California, USA

    Leslie Z. Benet Ph.D., Pharm.D.(Hon.) (Professor and Chairman) (Professor and Chairman)

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© 1993 Springer Science+Business Media New York

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Leal, M., Yacobi, A., Batra, V.K. (1993). Use of Toxicokinetic Principles in Drug Development: Bridging Preclinical and Clinical Studies. In: Yacobi, A., Skelly, J.P., Shah, V.P., Benet, L.Z. (eds) Integration of Pharmacokinetics, Pharmacodynamics, and Toxicokinetics in Rational Drug Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1520-0_8

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  • DOI: https://doi.org/10.1007/978-1-4757-1520-0_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1522-4

  • Online ISBN: 978-1-4757-1520-0

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