Safety pharmacology methods and models in an evolving regulatory environment.


:This editorial prefaces the annual themed issue on safety pharmacology (SP) methods published in the Journal of Pharmacological and Toxicological Methods (JPTM). We highlight here the content derived from the recent 2016 Safety Pharmacology Society (SPS), Canadian Society of Pharmacology and Therapeutics (CSPT), and Japanese Safety Pharmacology Society (JSPS) joint meeting held in Vancouver, B.C., Canada. This issue of JPTM continues the tradition of providing a publication summary of articles primarily presented at the joint meeting with direct bearing on the discipline of SP. As the regulatory landscape is expected to evolve with revision announced for the existing guidance document on non-clinical proarrhythmia risk assessment (ICHS7B) there is also imminent inception of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. Thus, the field of SP is dynamically progressing with characterization and implementation of numerous alternative non-clinical safety models. Novel method development and refinement in all areas of the discipline are reflected in the content.


Pugsley MK,de Korte T,Authier S,Huang H,Accardi MV,Curtis MJ




Has Abstract


2017-09-01 00:00:00












  • A multi-site comparison of in vivo safety pharmacology studies conducted to support ICH S7A & B regulatory submissions.

    abstract:INTRODUCTION:Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maint...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章,多中心研究


    authors: Ewart L,Milne A,Adkins D,Benjamin A,Bialecki R,Chen Y,Ericsson AC,Gardner S,Grant C,Lengel D,Lindgren S,Lowing S,Marks L,Moors J,Oldman K,Pietras M,Prior H,Punton J,Redfern WS,Salmond R,Skinner M,Some M,Stanto

    更新日期:2013-07-01 00:00:00

  • Isolated heart perfusion according to Langendorff---still viable in the new millennium.

    abstract::The isolated perfused mammalian heart preparation was established in 1897 by Oscar Langendorff. The method was developed on the basis of the isolated perfused frog heart established by Elias Cyon at the Carl Ludwig Institute of Physiology in Leipzig, Germany in 1866. Observations made using both methods at the end of ...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 历史文章,杂志文章,评审


    authors: Skrzypiec-Spring M,Grotthus B,Szelag A,Schulz R

    更新日期:2007-03-01 00:00:00

  • Radiological analysis of gastrointestinal dysmotility in a model of central nervous dopaminergic degeneration: comparative study with conventional in vivo techniques in the rat.

    abstract:INTRODUCTION:Gastrointestinal (GI) motility disorders include many clinical manifestations associated with various pathologies. They are widespread and can be considered a primary symptom or can be associated to other diseases, such as Parkinson's disease. Understanding the type and site of GI dysmotility is crucial to...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Vegezzi G,Al Harraq Z,Levandis G,Cerri S,Blandini F,Gnudi G,Miduri F,Blandizzi C,Domenichini G,Bertoni S,Ballabeni V,Barocelli E

    更新日期:2014-09-01 00:00:00

  • Epigenetic histone acetylation and deacetylation mechanisms in experimental models of neurodegenerative disorders.

    abstract:INTRODUCTION:Epigenetic modifications, such as histone acetylation and deacetylation, are responsible for maintaining chromatin stability. As such, they have been implicated in a wide range of neurodegenerative disorders. METHODS:Histone acetylation involves the presentation of an acetyl group to lysine residues at th...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章,评审


    authors: Konsoula Z,Barile FA

    更新日期:2012-11-01 00:00:00

  • Rapid HPLC assay with coulometric detection for norepinephrine and 3-methoxy-4-hydroxyphenylglycol in the mouse brain.

    abstract::For the rapid assay of norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) in the mouse brain, we developed a simple method using isocratic HPLC with coulometric detection. This method permits NE and MHPG assay within 5 min in one chromatographic run. Within-run coefficients of variati...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Murai S,Saito H,Masuda Y,Ohkubo N,Itoh T

    更新日期:1994-10-01 00:00:00

  • Cerulein-induced chronic pancreatitis in Swiss albino mice: An improved short-term model for pharmacological screening.

    abstract::There is a need for short-term, reliable and reproducible animal model of chronic pancreatitis (CP) in small animals like mice. This study was aimed to establish the 9 exposures of cerulein-induced CP in mice. Repeated intraperitoneal cerulein injections were performed at 6 consecutive doses (50 μg/kg)/day, 3 days a w...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Bansod S,Khurana A,Godugu C

    更新日期:2019-01-01 00:00:00

  • To establish a pharmacological experimental platform for the study of cardiac hypoxia using the microelectrode array.

    abstract:INTRODUCTION:Simultaneous recording of electrical potentials from multiple cells may be useful for physiological and pharmacological research. The present study aimed to establish an in vitro cardiac hypoxia experimental platform on the microelectrode array (MEA). METHODS:Embryonic rat cardiac myocytes were cultured o...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Yeung CK,Sommerhage F,Wrobel G,Law JK,Offenhäusser A,Rudd JA,Ingebrandt S,Chan M

    更新日期:2009-05-01 00:00:00

  • A simple, automatic method for morphometric analysis of the left ventricle in rats with myocardial infarction.

    abstract::Induction of acute myocardial infarction in the rat is an established model for studying effects of therapeutic interventions. Images of sections of the rat left ventricle, stained with nitroblue tetrazolium, were digitized and several parameters estimated by dedicated software on an image analyzer (IBAS 2.0). The met...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Porzio S,Masseroli M,Messori A,Forloni G,Olivetti G,Jeremic G,Riva E,Luvarà G,Latini R

    更新日期:1995-08-01 00:00:00

  • An overview of the safety pharmacology career of Dr. C.R. Hassler.

    abstract::Each year the Safety Pharmacology Society (SPS) recognizes an investigator who has had a marked impact upon the discipline. The 2016 recipient of the SPS Distinguished Service Award (DSA) was Dr. Craig R. Hassler. Dr. Hassler is one of the founding members of the SPS and has been actively engaged in physiological rese...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 传,历史文章,杂志文章


    authors: Hawk MA,Pugsley MK,Vinci T,Wallery J,Hassler CR,Hamlin RL

    更新日期:2017-09-01 00:00:00

  • Isolation of liver nuclei that retain functional trans-membrane transport.

    abstract::We have developed a method for the rapid isolation of hepatocyte nuclei, which employs gentle homogenization and centrifugation conditions, and involves minimal processing time. The purified nuclei were morphologically unaltered when observed by light and electron microscopy. No significant contamination from cytoplas...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Ho YF,Guenthner TM

    更新日期:1997-11-01 00:00:00

  • Origins, practices and future of safety pharmacology.

    abstract::The origins of safety pharmacology are grounded upon observations that organ functions (like organ structures) can be toxicological targets in humans exposed to novel therapeutic agents, and that drug effects on organ functions (unlike organ structures) are not readily detected by standard toxicological testing. Safet...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章,评审


    authors: Bass A,Kinter L,Williams P

    更新日期:2004-05-01 00:00:00

  • A simple method for the quantitative evaluation of neuromuscular blockade in mice.

    abstract::The purpose of this study was to develop a simple and noninvasive method for the quantitative evaluation of neuromuscular blockade in mice. The sciatic nerve in anesthetized animals (etomidate, 50 mg/kg or mephenesin, 250 mg/kg) was stimulated using transcutaneous electrodes; repetitive supramaximal stimulations (3 Hz...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Lefebvre HP,Cardona A,Toutain PL,Morel E,Bach JF,Vernet-der-Garabedian B

    更新日期:1992-05-01 00:00:00

  • Possible use of excretion of tubular epithelial cells for the study of the nephrotoxic effect of xenobiotics.

    abstract::The method of determination of the minute excretion of tubular epithelial cells renders it possible to investigate the course of the nephrotoxic effect of the toxin by the influence of which excretion of tubular round epithelial cells is increased. The nephrotoxic effect of repeated administration of amphotericin B (1...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Stĕtinová V,Trejtnar F,Kopecký J,Grossmann V,Kvètina J,Kopecká L,Semecký V

    更新日期:1996-12-01 00:00:00

  • A simple method for measuring the effects of drugs on intestinal longitudinal and circular muscle.

    abstract::A tissue preparation is described which makes it possible to examine the effect of drugs on the nerves that control both longitudinal and circular muscles of the small intestine. The preparation consists of a segment of rat ileum set up to measure the tension developed in the longitudinal muscle and intraluminal press...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Coupar IM,Liu L

    更新日期:1996-11-01 00:00:00

  • A high-throughput colorimetric-based bioassay method for determination of fosmidomycin in plasma and urine and application for pharmacokinetic study.

    abstract:INTRODUCTION:Fosmidomycin is a phosphonic acid derivative originally isolated as a natural antibiotic from Streptomyces lavendulae. It was originally used as an antibiotic, and later on as an antimalarial drug. A simple, sensitive, selective and reproducible bioassay based on colorimetric method was developed for the d...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Cheoymang A,Na-Bangchang K

    更新日期:2010-05-01 00:00:00

  • A framework to assess the translation of safety pharmacology data to humans.

    abstract::This article outlines a strategy for collecting accurate data for the determination of the sensitivity, specificity and predictive value of safety pharmacology models. This entails performing a retrospective analysis on commonly used safety pharmacology endpoints and an objective assessment of new non-clinical models....

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Valentin JP,Bialecki R,Ewart L,Hammond T,Leishmann D,Lindgren S,Martinez V,Pollard C,Redfern W,Wallis R

    更新日期:2009-09-01 00:00:00

  • Ventricular cycle length irregularity affects the correlation between ventricular rate and coronary flow in isolated, Langendorff perfused guinea pig hearts.

    abstract:INTRODUCTION:Heart rate affects coronary flow, but the mechanism is complex. The relationship between rhythm and flow is unclear, especially in experimental settings used for determining drug actions. The present study examined whether ventricular irregularity influences coronary flow independently of heart rate. METH...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Takács H,Kui P,Farkas AS,Sarusi A,Forster T,Papp JG,Varró A,Curtis MJ,Shattock MJ,Farkas A

    更新日期:2016-01-01 00:00:00

  • Influence of surgically implantable telemetry solutions on in-life and post-mortem toxicology endpoints.

    abstract:INTRODUCTION:Understanding the appropriate application of telemetry and other technologies for nonclinical investigation of functional safety issues in the context of ongoing toxicology evaluations is a current industry challenge. One major issue is related to the potential impact of surgical implantation of a telemetr...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Baird TJ,Bailie M,Patrick DJ,Moddrelle D,Yoder J,Gauvin DV,Dalton JA

    更新日期:2013-05-01 00:00:00

  • Comparison of freely-moving telemetry Chinese Miniature Experiment Pigs (CMEPs) to beagle dogs in cardiovascular safety pharmacology studies.

    abstract:INTRODUCTION:Telemetry beagle dogs are the most frequently used species in cardiovascular telemetry assessments. However, beagle dogs may not be always suitable for all of the tests. Recently minipigs have received increased attention for these studies. Differences between the two species regarding the response of thei...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Yuan H,Zhao J,Guo J,Wu R,He L,Cui Y,Feng M,Zhang T,Hou M,Guo Q,Zhang L,Jia L,Huang C,Ye L,Peng S

    更新日期:2014-07-01 00:00:00

  • Adaptation to a blood pressure telemetry system revealed by measures of activity, agility and operant learning in mice.

    abstract:INTRODUCTION:Implantable telemetry enables continuous monitoring of physiological functions in freely moving animals and can greatly complement pharmacological research. Despite its miniaturization, a sensor/transmitter constitutes 5% or more of a mouse's bodyweight. The aim of the present study was to evaluate whether...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Popova A,Tsvirkun D,Dolgov O,Anokhin K,Alberts J,Lagereva E,Custaud MA,Gauquelin-Koch G,Vinogradova O,Andreev-Andrievskiy A

    更新日期:2017-01-01 00:00:00

  • Conscious and anesthetized non-human primate safety pharmacology models: hemodynamic sensitivity comparison.

    abstract:INTRODUCTION:Drug-induced cardiovascular effects identified in conscious cynomolgus monkeys equipped with tethers and prepared for radiotelemetry were compared with results from anesthetized non-human primate (cynomolgus and rhesus) models. METHODS:Remifentanil (4.0 microg/kg, bolus), esmolol (2.0 mg/kg, bolus) and do...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Authier S,Tanguay JF,Fournier S,Gauvin D,Legaspi M,Chaurand F,Breault C,Troncy E

    更新日期:2008-09-01 00:00:00

  • Washout of heme-containing proteins dramatically improves tetrazolium-based infarct staining.

    abstract:INTRODUCTION:Methods to determine infarct size following ischemia-reperfusion injury include gross staining with triphenyltetrazolium chloride (TTC) and perfusion of colored dyes to demarcate the non-ischemic zone. Infarcted tissue (INF) can typically appear a mottled tan to brownish color, making a border between INF ...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Pitts KR,Stiko A,Buetow B,Lott F,Guo P,Virca D,Toombs CF

    更新日期:2007-03-01 00:00:00

  • Hybridization buffer systems impact the quality of filter array data.

    abstract:INTRODUCTION:cDNA microarray technology has greatly facilitated mechanistic studies in pharmacology and toxicology. A clean hybridization with minimal background is critical for successful microarray analysis and is highly desired. However, clean hybridization alone is not enough; verification is needed. METHODS:Total...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Liu J,Walker N,Waalkes MP

    更新日期:2004-07-01 00:00:00

  • Development of a method to determine cytochrome P450 1A2, 2C9, 2D6 and 3A4 activity sheep hepatic microsomes.

    abstract:INTRODUCTION:Ex vivo studies of human fetal hepatic drug metabolism are uncommon as it requires access to functional liver tissue and therefore raises practical and ethical concerns. Large animal models provide an alternative opportunity to study changes in cytochrome P450 (CYP) activity in the mother and fetus during ...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: McBride GM,Soo JY,Varcoe T,Morrison JL,Wiese MD

    更新日期:2020-01-01 00:00:00

  • Antibodies to a synthetic peptide that react with flavin-containing monooxygenase (HLFMO3) in human hepatic microsomes.

    abstract::Flavin-containing monooxygenases (FMOs) catalyze the oxidation of a diverse array of xenobiotic compounds. The purpose of this investigation was to develop a specific immunological probe to human hepatic flavin-containing monooxygenase (HLFMO3). An oligopetide corresponding to amino acid residues 257-270 of HLFMO3 was...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Myers CR,Porgilsson B,Myers JM

    更新日期:1997-03-01 00:00:00

  • The influence of vancomycin concentration and the pH of plasma on vancomycin protein binding.

    abstract::A review of numerous studies of the protein binding of vancomycin suggests major discrepancies among their results. The reported percent protein binding of vancomycin varies from 0% to 98%. The influence of pH and concentration on the protein binding of vancomycin was investigated in this study. There was a significan...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Chen Y,Norris RL,Schneider JJ,Ravenscroft PJ

    更新日期:1992-08-01 00:00:00

  • The PEG-switch assay: a fast semi-quantitative method to determine protein reversible cysteine oxidation.

    abstract:INTRODUCTION:Reversible protein cysteine oxidation is recognised as a pivotal post-transitional modification that transduces physiological as well as pathological signalling. Pharmacological interventions that target specific sources of oxidant formation are currently being trialled to ascertain their potential ability...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Burgoyne JR,Oviosu O,Eaton P

    更新日期:2013-11-01 00:00:00

  • L-type calcium channel antagonism - Translation from in vitro to in vivo.

    abstract:INTRODUCTION:Although therapeutically beneficial in the treatment of certain diseases, L-type calcium channel antagonism can result in unwanted off-target pharmacology leading to adverse drug reactions and to the termination of the development of otherwise promising compounds. In the present study three marketed calciu...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Fermini B,Ramirez DS,Sun S,Bassyouni A,Hemkens M,Wisialowski T,Jenkinson S

    更新日期:2017-01-01 00:00:00

  • Effects of passage number on proliferation and store-operated calcium entry in A7r5 vascular smooth muscle cells.

    abstract:INTRODUCTION:Embryonic rat aortic smooth muscle cells, A7r5, have been used extensively as an in vitro vascular smooth muscle cell model. They are usually provided at 11th passage by supplier and generally used before 25th passage. However, the exact passage number (P#) used is not reported in general. METHODS:In this...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Erac Y,Selli C,Filik P,Tosun M

    更新日期:2014-07-01 00:00:00

  • Cholemic transgenic mice: a novel animal model to investigate the effects of bile acids.

    abstract:INTRODUCTION:Laboratory investigations into cholestatic liver disease and the effects of cholemia on organ function are long-standing subjects of scientific enquiry. A widely-used strategy to investigate these topics relies on animal-based research using experimental animal models. Targeted inactivation of the spgp gen...

    journal_title:Journal of pharmacological and toxicological methods

    pub_type: 杂志文章


    authors: Ljubuncic P,Yousef I,Bomzon A

    更新日期:2004-11-01 00:00:00