abstract：INTRODUCTION:The analytical solutions to compartmental pharmacokinetic models are well known, but have not been presented in a form that easily allows for complex dosing regimen and changes in covariate/parameter values that may occur at discrete times within and/or between dosing intervals. METHODS:Laplace transforms...

journal_title：Journal of pharmacological and toxicological methods

authors： Abuhelwa AY,Foster DJ,Upton RN

更新日期：2015-05-01 00:00:00

abstract：INTRODUCTION:Quantification of lactate dehydrogenase (LDH) release is a widely accepted assay for the quantitative determination of cell viability and late-stage apoptosis. Major disadvantages of commercially available LDH assay kits include proprietary formulations, limited options for optimization and high cost, all ...

journal_title：Journal of pharmacological and toxicological methods

authors： Kaja S,Payne AJ,Singh T,Ghuman JK,Sieck EG,Koulen P

更新日期：2015-05-01 00:00:00

abstract：INTRODUCTION:Inhalation of antigen in atopic asthma induces early (EAR) and late asthmatic responses (LARs), inflammatory cell infiltration and airways hyperresponsiveness (AHR). Previously, we have established a protocol of sensitisation and subsequent ovalbumin (Ova) inhalation challenge in guinea-pigs which induced ...

journal_title：Journal of pharmacological and toxicological methods

authors： Lowe AP,Broadley KJ,Nials AT,Ford WR,Kidd EJ

更新日期：2015-03-01 00:00:00

abstract：INTRODUCTION:A custom designed HD exposure system was used to deliver controlled inhaled doses to an animal model through an endotracheal tube. METHODS:Target HD vapor challenges were generated by a temperature controlled bubbler/aerosol trap, while concentration was monitored near real-time by gas chromatography. Ani...

journal_title：Journal of pharmacological and toxicological methods

authors： Perry MR,Benson EM,Kohne JW,Plahovinsak JL,Babin MC,Platoff GE Jr,Yeung DT

更新日期：2015-01-01 00:00:00

abstract：INTRODUCTION:RL-14 cells, human fetal ventricular cardiomyocytes, are a commercially available cell line that has been established from non-proliferating primary cultures derived from human fetal heart tissue. However, the expression of different drug metabolizing enzymes (DMEs) in RL-14 cells has not been elucidated y...

journal_title：Journal of pharmacological and toxicological methods

authors： Maayah ZH,Elshenawy OH,Althurwi HN,Abdelhamid G,El-Kadi AO

更新日期：2015-01-01 00:00:00

abstract：INTRODUCTION:Excitation of Acetylcholine-mediated (Ach) transmission (especially if irreversible) may pose life-threatening adverse events by increasing neuronal network activity. Unfortunately, adequate detection of this liability during early drug development is hampered, because published ex vivo electrophysiologica...

journal_title：Journal of pharmacological and toxicological methods

authors： Hermann D,van Amsterdam C

更新日期：2015-01-01 00:00:00

abstract：INTRODUCTION:In vivo profiles of aldosterone synthase inhibitors (ASIs) have been investigated utilizing various rodent models. Due to lack of CYP17 activity, rodents produce corticosterone rather than cortisol as that of humans, which raised concern to their effectiveness in translational pharmacological characterizat...

journal_title：Journal of pharmacological and toxicological methods

authors： Cai TQ,Stribling S,Tong X,Xu L,Wisniewski T,Fontenot JA,Struthers M,Akinsanya KO

更新日期：2015-01-01 00:00:00

abstract：:The objective of this research is to determine whether the administration of a complete soft food formula to sub-lethal irradiated animals from three different transgenic mouse strains over a period of 21 consecutive days will have a significant impact on the clinical signs, and the general survival rate of the animal...

journal_title：Journal of pharmacological and toxicological methods

authors： Jumanca OI,Palmer J

更新日期：2015-01-01 00:00:00

abstract：INTRODUCTION:Dipeptidyl peptidases (DPPs) 8 and 9 are homologous, cytoplasmic postproline-cutting enzymes, which have similar enzymatic activity and preferred substrates as DPP4. DPP4 is a well-known target for treating diabetes mellitus. With the increased concern of non-selectivity and toxicities caused by DPP4 inhib...

journal_title：Journal of pharmacological and toxicological methods

authors： Huan Y,Jiang Q,Liu JL,Shen ZF

更新日期：2015-01-01 00:00:00

abstract：:"What do you know about Safety Pharmacology?" This is the question that was asked in 2000 with the inception of the Safety Pharmacology Society (SPS). There is now a widespread awareness of the role of safety pharmacology in drug discovery and increasing awareness among the wider community of methods and models used i...

journal_title：Journal of pharmacological and toxicological methods

authors： Pugsley MK,Dalton JA,Authier S,Curtis MJ

更新日期：2014-09-01 00:00:00

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

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

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

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

更新日期：2014-07-01 00:00:00

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

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

abstract：INTRODUCTION:Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed. METHODS:A literature review was performed on computational models for hepatotoxicity (e.g. for drug-indu...

journal_title：Journal of pharmacological and toxicological methods

authors： Ekins S

更新日期：2014-03-01 00:00:00

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

authors： Burgoyne JR,Oviosu O,Eaton P

更新日期：2013-11-01 00:00:00

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

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

abstract：INTRODUCTION:In recent years, the anesthetized guinea pig has been used increasingly to evaluate the cardiovascular effects of drug-candidate molecules during lead optimization prior to conducting longer, more resource intensive safety pharmacology and toxicology studies. The aim of these studies was to evaluate the co...

journal_title：Journal of pharmacological and toxicological methods

authors： Morissette P,Nishida M,Trepakova E,Imredy J,Lagrutta A,Chaves A,Hoagland K,Hoe CM,Zrada MM,Travis JJ,Zingaro GJ,Gerenser P,Friedrichs G,Salata JJ

更新日期：2013-07-01 00:00:00

abstract：INTRODUCTION:Opioid withdrawal syndrome is a critical component of opioid abuse and consists of a wide array of symptoms including increases in pain sensitivity (hyperalgesia). A reliable preclinical model of hyperalgesia during opioid withdrawal is needed to evaluate possible interventions to alleviate withdrawal. The...

journal_title：Journal of pharmacological and toxicological methods

authors： Balter RE,Dykstra LA

更新日期：2013-05-01 00:00:00

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

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

abstract：INTRODUCTION:The pharmacological assessment of the factors for gastric protection of a test substance should involve experimental models that can determine the involvement of cytoprotective factors, as well as their influence on the secretion of hydrochloric acid. The original protocol of pylorus ligation in rats propo...

journal_title：Journal of pharmacological and toxicological methods

authors： Monteiro KM,Spindola HM,Possenti A,Tinti SV,Ruiz AL,Longato GB,Fiorito GF,Marchetti GM,Shiozawa L,Piloni BU,de Oliveira AC,Miyagawa LM,Carvalho JE

更新日期：2013-03-01 00:00:00

abstract：INTRODUCTION:IonWorks automated patch clamp systems are being widely used for ion channel drug discovery, but the perforated patch mode of these systems makes it difficult to obtain a steady intracellular Ca(2+) concentration ([Ca(2+)](i)). This difficulty prevents obtaining high-quality data regarding Ca(2+)-activated...

journal_title：Journal of pharmacological and toxicological methods

authors： Ido K,Ohwada T,Yasutomi E,Yoshinaga T,Arai T,Kato M,Sawada K

更新日期：2013-01-01 00:00:00

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

authors： Konsoula Z,Barile FA

更新日期：2012-11-01 00:00:00

abstract：INTRODUCTION:Bioimpedance spectroscopy (BIS) has been used in human and large animal research to assess body fluid compartment volumes (BFC) such as total body water (TBW), extracellular fluid volume (ECFV), and intracellular fluid volume (ICFV). To date, the application of BIS for determination of BFC in small researc...

journal_title：Journal of pharmacological and toxicological methods

authors： Hu L,Maslanik T,Zerebeckyj M,Plato CF

更新日期：2012-03-01 00:00:00

abstract：INTRODUCTION:The cytochrome P450 CYP26 family of retinoic acid (RA) metabolizing enzymes, comprising CYP26A1, CYP26B1, and CYP26C1 is critical for establishing patterns of RA distribution during embryonic development and retinoid homeostasis in the adult. All three members of this family can metabolize all trans-RA. CY...

journal_title：Journal of pharmacological and toxicological methods

authors： Helvig C,Taimi M,Cameron D,Jones G,Petkovich M

更新日期：2011-11-01 00:00:00

abstract：BACKGROUND:Animal models of allergy and bronchial hyperresponsiveness (BHR) are useful in researching pulmonary diseases and evaluating drug effects on the airways. Neonatally immunised rabbits exhibit several features of asthma as adults, including early and late airway responses following antigen challenge, oedema an...

journal_title：Journal of pharmacological and toxicological methods

authors： Keir SD,Spina D,Douglas G,Herd C,Page CP

更新日期：2011-09-01 00:00:00

abstract：:The use of animal models is an essential part of medical research and drug development. The essential skills required to be able to do such research includes experimental design, statistical analysis and the actual handling and treating of the animals (in vivo skills). The number of students in the U.K. receiving trai...

journal_title：Journal of pharmacological and toxicological methods

authors： King AJ,Bowe JE,Sprake JA,Kinchin IM

更新日期：2011-09-01 00:00:00

abstract：INTRODUCTION:The purpose of this study was: (1) to characterize and assess the incidence of spontaneous arrhythmias in totally naive Beagle dogs (n=51; 10 males+41 females): (2) to study the effects of permanent ECG- and LVP-probe telemetry implants both acutely and up to 233days after surgery in a subset of 11 female ...

journal_title：Journal of pharmacological and toxicological methods

authors： Cools F,Janssens S,Vanlommel A,Teisman A,Towart R,Gallacher DJ

更新日期：2011-07-01 00:00:00

abstract：INTRODUCTION:We characterised the development of Type 2 diabetes and associated changes in islet appearance in female ZDF rats and explored its suitability for studies with novel therapeutic agents. METHODS:Female ZDF rats were either chow or high fat (60%) fed for up to 36 days and blood glucose and plasma insulin co...

journal_title：Journal of pharmacological and toxicological methods

authors： Teague J,Gyte A,Peel JE,Young KC,Loxham SJ,Mayers RM,Poucher SM

更新日期：2011-01-01 00:00:00

abstract：:In this article we review the value and utility of the minipig as an animal model in regulatory toxicity testing. Our review is based on detailed consideration of the comparative biology of the minipig, and of the practical features of toxicity testing in the minipig. The minipig presents a favourable profile as a non...

journal_title：Journal of pharmacological and toxicological methods

authors： Bode G,Clausing P,Gervais F,Loegsted J,Luft J,Nogues V,Sims J,Steering Group of the RETHINK Project.

更新日期：2010-11-01 00:00:00

abstract：:Multiple ECG analysis strategies are used in safety pharmacology in a framework focused on accurate ECG complex interval quantification and arrhythmia detection. Automated arrhythmia detection is commonly used in the clinic and adapted tools may be used to facilitate analysis of large non-clinical datasets in safety p...

journal_title：Journal of pharmacological and toxicological methods

authors： Authier S,Pugsley MK,Troncy E,Curtis MJ

更新日期：2010-09-01 00:00:00

abstract：INTRODUCTION:Different methods for the analysis of behavioral observation data were compared to evaluate how the interpretation of a data set may depend on the analysis method employed. METHODS:Three methods of analysis were used to evaluate the same four sets of rodent behavioral FOB data: (1) evaluation by a trained...

journal_title：Journal of pharmacological and toxicological methods

authors： Markgraf CG,Cirino M,Meredith J

更新日期：2010-09-01 00:00:00

abstract：INTRODUCTION:The combined evaluation of physiology and behaviour allows a complete and more comprehensive pre-clinical assessment of central nervous system (CNS) function. An integrated video-telemetric electroencephalography (Video-tEEG) system, which allows the simultaneous and continuous recording of EEG and video i...

journal_title：Journal of pharmacological and toxicological methods

authors： Moscardo E,Rostello C

更新日期：2010-07-01 00:00:00

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

authors： Cheoymang A,Na-Bangchang K

更新日期：2010-05-01 00:00:00

abstract：:The majority of articles published in J Pharmacol Tox Methods describe new approaches, or modifications to those established (Curtis, 2006). However, even established methods have their limitations. It is part of the practice of research to troubleshoot: to identify methodological weaknesses and correct them. This pro...

journal_title：Journal of pharmacological and toxicological methods

authors： Curtis MJ

更新日期：2010-03-01 00:00:00

abstract：INTRODUCTION:The ability to quantify systemic concentrations of protein therapeutics is complicated by the presence of endogenous analyte, specific binding proteins, and nonspecific matrix components in biological matrices (Lee & Ma, 2007). Further complications can be introduced following pegylation whereby polyethyle...

journal_title：Journal of pharmacological and toxicological methods

authors： Myler HA,McVay S,Kratzsch J

更新日期：2010-03-01 00:00:00

abstract：INTRODUCTION:Increase of serum alanine aminotransferase (ALT) activity is widely used as a surrogate marker for tissue damage. Two ALT isoforms, ALT1 and ALT2, have been cloned recently in mammals. The study investigated the source of elevated ALT activity in serum of dogs treated with a hepatotoxic compound. METHODS:...

journal_title：Journal of pharmacological and toxicological methods

authors： Miyazaki M,Rosenblum JS,Kasahara Y,Nakagawa I,Patricelli MP

更新日期：2009-11-01 00:00:00

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

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

abstract：INTRODUCTION:Regulatory guidelines recommend the use of conscious, unrestrained animals for comprehensive cardiovascular safety assessment of a new therapeutic agent. Cardiovascular safety pharmacology studies normally use internal telemetry (surgical implants) in free-moving animals to monitor key ECG endpoints, like ...

journal_title：Journal of pharmacological and toxicological methods

authors： Chui RW,Fosdick A,Conner R,Jiang J,Bruenner BA,Vargas HM

更新日期：2009-07-01 00:00:00

abstract：INTRODUCTION:Evaluation of drug candidates in in-vitro assays of action potential duration (APD) is one component of preclinical safety assessment. Current assays are limited by technically-demanding, time-consuming electrophysiological methods. This study aimed to assess whether a voltage-sensitive dye-based assay cou...

journal_title：Journal of pharmacological and toxicological methods

authors： Hardy ME,Pollard CE,Small BG,Bridgland-Taylor M,Woods AJ,Valentin JP,Abi-Gerges N

更新日期：2009-07-01 00:00:00

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

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