Pharmacokinetics and pharmacodynamics in toxicology.
1. Pharmacokinetics aids interpretation of the dose-response relationship in individual toxicology studies. 2. When used to compare across studies, even in a single species other factors, including variation in pharmacodynamic response, must be taken into account. Variation in pharmacodynamic response becomes more profound when one compares across species. 3. Examples do occur where plasma concentration-response relationships are constant across species, particularly when corrected for unbound drug. These examples should not be taken as support, however, of a general universal principle. 4. Owing to multiple factors such as species differences in receptors, enzymes and ion channels, dose or plasma concentration-response relationships can vary enormously across species. In the light of this, the results of toxicology studies should be viewed as qualitative rather than quantitative. Once sufficient clinical experience is gained the human database is the overriding measure of drug safety.
Smith
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Department of Drug Metabolism, Pfizer Central Research, Sandwich, UK.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010599:Pharmacokinetics; D010600:Pharmacology; D013045:Species Specificity; D014116:Toxicology