Unit

UNIT 10.1 Overview of Safety Pharmacology

  1. Roger D. Porsolt

Published Online: 1 APR 2006

DOI: 10.1002/0471141755.ph1001s32

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Porsolt, R. D. 2006. Overview of Safety Pharmacology. Current Protocols in Pharmacology. 32:10.1:10.1.1–10.1.6.

Author Information

  1. Porsolt & Partners Pharmacology, Boulogne-Billancourt, France

Publication History

  1. Published Online: 1 APR 2006
  2. Published Print: MAR 2006

This is not the most recent version of the article. View current version (2 DEC 2013)

Abstract

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 CO2. Other aspects of safety pharmacology studies discussed are the timing of studies, ethical and animal welfare issues, and statistical evaluation.

Keywords:

  • safety pharmacology;
  • risk assessment;
  • ICH S7A guidelines;
  • central nervous system;
  • cardiovascular system;
  • respiratory system