Overview of safety pharmacology.

Safety pharmacology assesses the potential risks of novel pharmaceuticals for human use. ICH S7A guidelines recommend a core battery of studies on three vital systems: central nervous system (CNS), cardiovascular (CV) and respiratory. Primary CNS studies look for effects on general behavior, locomotion, neuromuscular coordination, the convulsive threshold, and vigilance. The primary CV test battery evaluates proarrhythmic risk using in vitro approaches (hERG channel and Purkinje fiber assays) and in vivo measurements in conscious animals via telemetry. Comprehensive cardiac risk assessment also includes full hemodynamic evaluation, most suitably conducted in the anesthetized large animal. Basic respiratory function can be approached via whole-body plethysmography in conscious animals where sensitivity to respiratory-depressant effects can be enhanced by exposure to increased CO(2). Other aspects of safety pharmacology studies discussed are the timing of studies, ethical and animal welfare issues, and statistical evaluation.