Primary pharmacodynamics

Doses should include and exceed primary pharmacodynamic or therapeutic range. 

Primary pharmacodynamic studies investigate the mode of action or effects of a substance in relation to its desired therapeutic target. 

For early clinical trials, where it is unlikely there will be full reproductive toxicology data, any application should include a discussion of whether any effects on reproduction can be anticipated from the primary pharmacodynamics. The nature of the target receptor binding and any potential for binding to receptors involved in reproduction should be considered. For compounds in classes already known to be teratogenic such as cytotoxic anticancer products, retinoids, or histone deacetylase inhibitors, it can be reasonably expected that... 

In simple terms, there are four primary pharmacodynamic models that have been widely used. These are as follows ... 

Pharmacology studies can be divided into three categories primary pharmacodynamic, secondary... 

A subsection on Primary Pharmacodynamics (i.e., studies on the mode of action and/or effects of a drug candidate in relation to the desired therapeutic target) should, when possible, relate the pharmacology of a drug candidate to available data (e.g., selectivity, safety, potency) on other drugs in... 

Pharmacologically mediated adverse effects can be placed into one of three categories (1) primary pharmacodynamic (PD) effects, (2) secondary PD effects, and (3)those either not linked to the primary PD effect or caused by an unknown mechanism. Primary pharmacodynamic adverse effects are those which represent an overexpression of the primary, intended pharmacological effect of the xenobi-otic. An example of an adverse primary PD effect occurs when an overdose of insulin, a critical hormone involved in the homeostasis of blood glucose, is administered. A deficiency of insulin results in diabetes mellitus and is expressed by hyperglycemia. Overdosing of insulin results in hypoglycemia, which can have immediate and severe clinical consequences. 

In addition to the categorizations described above, two other categories of pharmacodynamic studies were described in the ICH S7A guidelines at the request of ICH M4S EWG (Anon 2001a, d). These included the primary pharmacodynamic and secondary pharmacodynamic smdies, which were described in order to distinguish the requirement for GLP compliance for safety pharmacology smdies, but not for primary or secondary pharmacodynamic smdies. 

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