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

  • Mauricio Leal
  • Avraham Yacobi
  • Vijay K. Batra


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.


Peak Plasma Concentration Hepatic Blood Flow Brain Weight Oral Clearance Allometric Relationship 
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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Mauricio Leal
    • 1
  • Avraham Yacobi
    • 1
  • Vijay K. Batra
    • 1
  1. 1.Medical Research DivisionAmerican Cyanamid CompanyPearl RiverUSA

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