ABSTRACT
INTRODUCTION AND DEFINITIONS In vitro and in vivo animal pharmacology studies (to show that a drug has efficacy and examining high-dose pharmacological effects) are a usual component of drug safety assessment, but until fairly recently the relationship between what was termed primary pharmacology, secondary pharmacology, and safety pharmacology or even general, ancillary, high-dose, or “regulatory” pharmacology was unclear. However, in recent years, regulatory guidance (ICH S7A) has appeared, which makes the situation clear, with the following definitions:! Primary pharmacology (pharmacodynamic) studies are those on the mode of action of a
drug in relation to its desired therapeutic effect.! Secondary pharmacology (pharmacodynamic) studies are those on the mode of action and/or effects of a drug not related to its desired therapeutic target.! Safety pharmacology studies are those that investigate the potential undesirable pharmacodynamic functions of a drug on physiological functions in relation to exposure in the therapeutic range and above. There is a need to: – relate the relevance of these undesirable properties to human safety. – evaluate adverse findings in toxicology/clinical studies. – investigate the mechanisms of adverse pharmacodynamic effects.
