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Title: Safety pharmacology — Current and emerging concepts

Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests.
Authors:
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  1. MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom)
  2. Lorraine University Pharmacolor Consultants Nancy PCN (France)
  3. UCB Pharma (Belgium)
  4. Sanofi-aventis (France)
  5. Astra-Zeneca (United Kingdom)
  6. Ruprecht-Karls-Universität Heidelberg (Germany)
  7. Huntingdon Life Sciences (United Kingdom)
  8. Boehringer-Ingelheim (Germany)
  9. Roche (Switzerland)
Publication Date:
OSTI Identifier:
22285504
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 273; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALANINES; ALKALINE PHOSPHATASE; BIOLOGICAL MARKERS; CENTRAL NERVOUS SYSTEM; CLINICAL TRIALS; GLUTATHIONE; HEART; KIDNEYS; LACTATE DEHYDROGENASE; NEUTROPHILS; PHARMACOLOGY; RISK ASSESSMENT; SAFETY; STEM CELLS