Pharmacokinetic Considerations in the Toxicologic Evaluation of Xenobiotics

  • Roger K. Verbeeck
Conference paper
Part of the NATO ASI Series book series (volume 93)

Abstract

Toxicokinetics can be defined as the kinetics of absorption, distribution and elimination (i.e. excretion and metabolism) of toxic substances, including therapeutic agents, in animal species used in experimental toxicology. Toxicokinetics is different from pharmacokinetics in that it describes the rates of absorption, distribution and elimination of xenobiotics at relatively high doses often associated with toxic effects. At these high doses the reversible binding of the xenobiotic to plasma and/or tissue proteins may become saturated, as well as the active transport systems and metabolizing enzymes. Consequently, in toxicokinetics one frequently encounters nonlinearity in these rate processes leading to dose-dependent kinetics. This is in contrast to the pharmacokinetic behavior of most drugs following administration of therapeutic doses which usually can be described in terms of linear kinetics. Another important factor which can account or contribute to dose-dependent toxicokinetic behavior of xenobiotics is the potential interaction of the xenobiotic and/or its metabolites with physiological processes such as regional blood flow, urine pH, gastric emptying, etc (Table 1).

Keywords

Toxicity Nicotine Indomethacin Paracetamol Acetaminophen 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Roger K. Verbeeck
    • 1
  1. 1.Pharmacokinetics and Drug Metabolism Laboratory, School of PharmacyCatholic University of LouvainBrusselsBelgium

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