title: Safety pharmacology--current and emerging concepts.
abstract: 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.
authors.affiliation: MRC Centre for Drug Safety Science, University of Liverpool, UK.
authors.forename: Junnat
authors.initials: J
authors.lastname: Hamdam
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Sethu
authors.forename: Trevor
authors.initials: T
authors.lastname: Smith
authors.forename: Ana
authors.initials: A
authors.lastname: Alfirevic
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alhaidari
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Atkinson
authors.forename: Mimieveshiofuo
authors.initials: M
authors.lastname: Ayala
authors.forename: Helen
authors.initials: H
authors.lastname: Box
authors.forename: Michael
authors.initials: M
authors.lastname: Cross
authors.forename: Annie
authors.initials: A
authors.lastname: Delaunois
authors.forename: Ailsa
authors.initials: A
authors.lastname: Dermody
authors.forename: Karthik
authors.initials: K
authors.lastname: Govindappa
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Guillon
authors.forename: Rosalind
authors.initials: R
authors.lastname: Jenkins
authors.forename: Gerry
authors.initials: G
authors.lastname: Kenna
authors.forename: Björn
authors.initials: B
authors.lastname: Lemmer
authors.forename: Ken
authors.initials: K
authors.lastname: Meecham
authors.forename: Adedamola
authors.initials: A
authors.lastname: Olayanju
authors.forename: Sabine
authors.initials: S
authors.lastname: Pestel
authors.forename: Andreas
authors.initials: A
authors.lastname: Rothfuss
authors.forename: James
authors.initials: J
authors.lastname: Sidaway
authors.forename: Rowena
authors.initials: R
authors.lastname: Sison-Young
authors.forename: Emma
authors.initials: E
authors.lastname: Smith
authors.forename: Richard
authors.initials: R
authors.lastname: Stebbings
authors.forename: Yulia
authors.initials: Y
authors.lastname: Tingle
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Valentin
authors.forename: Awel
authors.initials: A
authors.lastname: Williams
authors.forename: Dominic
authors.initials: D
authors.lastname: Williams
authors.forename: Kevin
authors.initials: K
authors.lastname: Park
authors.forename: Christopher
authors.initials: C
authors.lastname: Goldring
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods / Q000592:standards* / Q000639:trends; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000592:standards / Q000639:trends; D004347:Drug Interactions / Q000502:physiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism / Q000592:standards*
chemical_list: D004364:Pharmaceutical Preparations
keywords: ADR; AKI; ALP; ALT; AP; AST; Adverse Drug Reaction; BP; BUN; CLU; CNS; CVS; Cardiovascular; Cardiovascular System; Central Nervous System; Central nervous system; ECG; EEG; EMA; Electrocardiogram; European Medicines Agency; FDA; FOB; Food and Drug Administration; Functional Observation Battery; GFR; GGT; GI; GST; Gastrointestinal; Glomerular Filtration Rate; HR; ICH; International Conference on Harmonisation; KIM-1; LDH; N-acetyl-β-d-glucosaminidase; NCE; NGAL; NMR; Neutrophil gelatinase-associated lipocalin; New Chemical Entity; Nuclear Magnetic Resonance; PBPK; PEB; RPA-1; Respiratory; Risk; SP; Safety Pharmacology; Safety pharmacology; TFF3; VQM; Ventilation (V)/perfusion (Q) mismatch (M); action potential; acute kidney injury; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; blood pressure; blood urea nitrogen; clusterin; electroencephalography; glutathione S transferase; hERG; hESC; heart rate; human Ether-a-go-go related gene; human embryonic stem cells; kidney injury molecule-1; lactate dehydrogenase; miR; microRNA; photoelectric beam interruption technique; physiologically based pharmacokinetics; renal papillary antigen-1; trefoil factor 3; β-NAG; γ-glutamyl transferase