Methodology used in safety pharmacology: Appraisal of the state-of-the-art, the regulatory issues and new directions

Abstract

This is the second focused issue of the Journal of Pharmacological and Toxicological Methods that is devoted exclusively to methodology, opinions and regulatory issues related to Safety Pharmacology. This issue of the Journal highlights a record number of articles and abstracts from the 4th Annual Safety Pharmacology Society (SPS) meeting that was held in Covington, Kentucky September 27–29, 2004. The focus of this issue of the Journal is to present a description of currently used fundamental pharmacological methods as outlined in the regulatory guidance documents for pre-clinical safety testing of drugs (ICH S7A and S7B). This issue features articles that discuss methods related to in vivo and in vitro CNS, respiratory and cardiovascular core battery studies. Additionally, articles are included that discuss species differences and recording issues in EKG measurement; automated (HTS) electrophysiology methods for assessing drug-induced hERG blockade (i.e., PatchXpress 7000A and hERG-lite®); methods that describe and validate the use of the guinea pig as a safety pharmacology screening model; methods used to predict QTc prolongation and mathematical models that describe beat-to-beat instability of QT duration; supplemental studies that assess and discuss emerging renal biomarkers and renal function and food effects on gastrointestinal transit time; pro-arrhythmia models, cardiac function assessment using 3-D echocardiography and a description of a novel open field motor activity system to assess the possible CNS effects of drugs. Thus, this issue of the Journal of Pharmacological and Toxicological Methods should be a primary resource aid to individuals in academia and industry that are interested in understanding Safety Pharmacology methods. It provides a comprehensive overview of current and advanced methods used in Safety Pharmacology studies today.