Basic principles of non-clinical development

Pharmacodynamics studies aim to address - these studies are explained below:

• Primary pharmacodynamics.
• Secondary pharmacodynamics.
• Safety pharmacology.
• Pharmacodynamic interactions.
  

Primary pharmacodynamics

The goal of primary PD studies is to find the mode of action or effects that are related to the desired therapeutic target (efficacy). These studies:

• Use one or more pharmacological animal models of the disease.
• Help find the best candidate for further development.
• Help select doses for both non-clinical and clinical studies.

The studies can be done in-vivo and/or in-vitro. They are generally conducted during the discovery phase and are usually non-GLP (not done according to Good Laboratory Practice (GLP)).

Secondary pharmacodynamics

The goal of secondary PD studies is to find the mode of action or effects that are not related to the desired therapeutic target. Secondary PD studies may not be needed if literature can give the necessary information instead.

Safety pharmacology

• The objective is to identify unwanted effects on key physiological functions within the therapeutic dose range and higher. Usual studies look into respiratory, central nervous system (CNS), and cardiovascular functions. Studies on respiratory and CNS (e.g. functional observational battery (FOB)) functions are usually performed on rats (in vivo).
• Studies on cardiovascular function are performed in vitro (e.g. human ether-a-go-go related gene (hERG)) and in-vivo (e.g. dogs with telemetry).
• Follow-up studies may be needed if concerns arise.

These studies must be conducted following Good Laboratory Practice (GLP). To reduce the use of animals, the testing should be done in vitro where this is possible.