Abstract

Pharmacodynamics concerns the relationship between drug concentration and intensity of pharmacologic effect. It includes the exploration and assessment of relevant variables such as pharmacologically active metabolites, pharmacodynamic drug interactions and effects of genetics and underlying diseases. Available (though limited) information indicates that drug concentrations required to produce a defined intensity of pharmacologic action are quite similar in man and animals. For such interspecies comparisons, consideration must be given to possible differences in drug-protein binding, active metabolites, kinetics of equilibration of drug between plasma and biophase, and definition of the pharmacologic endpoint. It is now evident that many unanticipated, pharmacodynamically relevant clinical risk factors, including some that have caused a substantial number of deaths, could have been recognized in preclinical pharmacodynamic studies. Examples based on studies in the author’s laboratory include potentiation of barbiturates in renal failure, increased response to benzodiazepines in severe liver disease, increased neurotoxicity of theophylline in renal failure, increased potency of general anesthetics in hemorrhagic hypovolemia, and the steep responder syndrome in warfarin therapy. Preclinical pharmacodynamics provides a means for identifying, in advance of clinical use, potential risk factors and conditions under which drugs may be subject to profound changes in their concentration-effect relationships.

Keywords

Unbind Drug Pharmacodynamic Model Drug Development Process Pearl Harbor Interspecies Comparison 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Gerhard Levy
    • 1
  1. 1.Department of Pharmaceutics, School of PharmacyState University of New York at BuffaloAmherstUSA

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