Journal of pharmacological and toxicological methods最新文献

{"title":"Comparing the sensitivity of cross-over and parallel study designs for QTc assessment: An analysis based on a single large study of moxifloxacin in 48 nonhuman primates","authors":"Derek J. Leishman ,&nbsp;David L. Holdsworth ,&nbsp;Derek D. Best ,&nbsp;Brian M. Roche","doi":"10.1016/j.vascn.2023.107299","DOIUrl":"10.1016/j.vascn.2023.107299","url":null,"abstract":"<div><p><span>The cardiovascular safety pharmacology (SP) study conducted to satisfy ICH S7A and S7B has commonly used a cross-over study design where each animal receives all treatments. In an increasing number of cases, cross-over designs are not possible and parallel studies have to be used. These can seldom be as large as 8 animals/treatment to match an </span><em>n</em> = 8 cross-over. Animals in parallel designs receive only one treatment. Parallel studies will have a different sensitivity to detect changes. This sensitivity is a critical question in using nonclinical QTc evaluations to support an integrated proarrhythmic risk assessment under the newly released ICH E14/S7B Q&amp;As. The current analysis used a study large enough (<em>n</em> = 48) to be analyzed both as a parallel and as a cross-over design to directly compare the performance of the two experimental designs coupled to different statistical models, while all other study conduct aspects were the same.</p><p><span>A total of 48 nonhuman primates (NHP) received 2 different treatments twice: vehicle, moxifloxacin (80 mg/kg), vehicle, moxifloxacin (80 mg/kg). Post-dose QTc interval data were recorded for 48 h for each treatment. Data were analyzed using 12 animals randomly selected for each treatment in a parallel design or as an </span><em>n</em> = 48 animal cross-over study. Different statistical models were used. The primary endpoint was the residual deviation (sigma) from the models applied to hourly time intervals. The sigma was used to determine the minimal detectable difference (MDD) for the study design-statistical model combination.</p><p>Two statistical models were applicable to either study design. They gave similar sigma and resulting MDD values. In cross-over designs, the individual animal identification (ID) can be used in the statistical model. This enabled the smallest MDD value. Simple statistical models for analysis were identified: Treatment + Baseline for parallel designs and Treatment + ID for cross-over designs.</p><p>The statistical sensitivity of NHP parallel study designs is reasonable (MDD for <em>n</em> = 6 of 12.7 ms), and in combination with testing exposures higher than likely to be necessary in man could be used in an integrated risk assessment. Where sensitivity of the NHP in vivo QTc assessment is critical, the cross-over design enabled a higher sensitivity (MDD 12.2 ms for <em>n</em> = 4; 8 ms for <em>n</em> = 8).</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptation of closed-chest infarction porcine model to adult Pannon minipigs","authors":"Dénes Kőrösi ,&nbsp;András Vorobcsuk ,&nbsp;Dániel Fajtai ,&nbsp;Ottó Tátrai ,&nbsp;Emőke Bodor ,&nbsp;Kornélia Farkas ,&nbsp;Rita Garamvölgyi","doi":"10.1016/j.vascn.2023.107469","DOIUrl":"10.1016/j.vascn.2023.107469","url":null,"abstract":"<div><p>The aim of the recent study was to collect data on the genotype characteristics of the Hungarian self-bred Pannon minipigs by adapting a standardized infarct model procedure. Closed chest AMI was induced by balloon occlusion for 90 min in the left anterior descendent coronary artery (LAD) in 24 adult intact female minipigs followed by reperfusion. To assess the left ventricular (LV) function, serial cardiac magnetic resonance imaging (cMRI) was performed prior to the experimental procedure, on day 3 post-AMI (72 ± 12 h), and at 1 month follow-up (Day 30 ± 2 days). Compared to baseline cMRI scans the end-diastolic volume (EDV) was increased on days 3 and 30 On day 3 the left ventricular ejection fraction (LVEF) decreased significantly but there was no statistical difference between the baseline and day 30 measurements. Cardiac output, stroke volume, and end-systolic volume significantly were increased compared to baseline on day 30 A high percentage (54%) of malignant arrhythmias occurred during the AMI procedure, with a 25% mortality rate. The compensatory capacity of the Pannon minipig heart is excellent therefore the use of different cardiac parameters and invasive measurements is advisable in chronic pharmacological experiments to complement cMRI data.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10450383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Appraisal of state-of-the-art” The 2021 Distinguished Service Award of the Safety Pharmacology Society: Reflecting on the past to tackle challenges ahead","authors":"Jean-Pierre Valentin,&nbsp;Alicia Sibony,&nbsp;Marie-Luce Rosseels,&nbsp;Annie Delaunois","doi":"10.1016/j.vascn.2023.107269","DOIUrl":"10.1016/j.vascn.2023.107269","url":null,"abstract":"<div><p>This appraisal of state-of-the-art manuscript highlights and expands upon the thoughts conveyed in the lecture of Dr. Jean-Pierre Valentin, recipient of the 2021 Distinguished Service Award of the Safety Pharmacology<span> Society, given on the 2nd December 2021. The article reflects on the strengths, weaknesses, opportunities, and threats that surrounded the evolution of safety and secondary pharmacology over the last 3 decades with a particular emphasis on pharmaceutical drug development delivery, scientific and technological innovation, complexities of regulatory framework and people leadership and development. The article further built on learnings from past experiences to tackle constantly emerging issues and evolving landscape whilst being cognizant of the challenges facing these disciplines in the broader drug development and societal context.</span></p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9486121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of bioanalysis of dried blood samples","authors":"Elham Ataei Alizadeh ,&nbsp;Georg Rast ,&nbsp;Chris Cantow ,&nbsp;Jessica Schiwon ,&nbsp;Florian Krause ,&nbsp;Guido R.Y. De Meyer ,&nbsp;Pieter-Jan Guns ,&nbsp;Brian D. Guth ,&nbsp;Michael Markert","doi":"10.1016/j.vascn.2023.107296","DOIUrl":"10.1016/j.vascn.2023.107296","url":null,"abstract":"<div><h3>Introduction</h3><p>Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development. Pharmacokinetic data are often obtained by taking multiple blood samples, which may disturb physiological parameters and complicate study designs. Wearable automatic blood sampling systems can improve this limitation by collecting dried blood samples at programmable time points without disrupting cardiovascular parameters. It is the objective of this study to evaluate the bioanalysis of DBS in comparison to conventional blood sampling techniques and to optimize the recovery of various compounds spiked into canine blood dried on filter paper tape.</p></div><div><h3>Methods</h3><p>Incubated blood samples from Beagle dogs were spiked with 16 different compounds and half of the whole blood sample was centrifuged to obtain plasma. After the dried blood sample drops were dried, liquid chromatography-mass spectrometry methods were used to analyze the samples. The study explored different anticoagulants, sample preparation methods and technical approaches to best determine the compound concentrations in dried blood samples.</p></div><div><h3>Results</h3><p>With the two anticoagulants tested and using the optimized sample preparation methods and technical approaches we employed, the bioanalysis of dried blood samples can provide equivalent results to conventional blood sampling techniques.</p></div><div><h3>Discussion</h3><p>Automated blood sampling systems have the potential to provide increased numbers of blood samples, providing substantially more Pharmacokinetic data within safety pharmacology studies without disrupting physiological parameters. They can provide a viable alternative to traditional methods of obtaining blood for various other types of studies or analyses.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10665735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Off-target pharmacological activity at various kinases: Potential functional and pathological side effects","authors":"Jonathon R. Green ,&nbsp;Prathap Kumar S. Mahalingaiah ,&nbsp;Sujatha M. Gopalakrishnan ,&nbsp;Michael J. Liguori ,&nbsp;Scott W. Mittelstadt ,&nbsp;Eric A.G. Blomme ,&nbsp;Terry R. Van Vleet","doi":"10.1016/j.vascn.2023.107468","DOIUrl":"10.1016/j.vascn.2023.107468","url":null,"abstract":"<div><p>In drug discovery, during the lead optimization and candidate characterization stages, novel small molecules are frequently evaluated in a battery of in vitro pharmacology assays to identify potential unintended, off-target interactions with various receptors, transporters, ion channels, and enzymes, including kinases. Furthermore, these screening panels may also provide utility at later stages of development to provide a mechanistic understanding of unexpected safety findings. Here, we present a compendium of the most likely functional and pathological outcomes associated with interaction(s) to a panel of 95 kinases based on an extensive curation of the scientific literature. This panel of kinases was designed by AbbVie based on safety-related data extracted from the literature, as well as from over 20 years of institutional knowledge generated from discovery efforts. For each kinase, the scientific literature was reviewed using online databases and the most often reported functional and pathological effects were summarized. This work should serve as a practical guide for small molecule drug discovery scientists and clinical investigators to predict and/or interpret adverse effects related to pharmacological interactions with these kinases.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10064816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of the bioanalytical methods used for the determination of benzodiazepines in biological samples and their suitability for emergency toxicological analysis","authors":"Mohamed Yafout,&nbsp;Rachid Aït Mouss,&nbsp;Houda Bouchafra,&nbsp;Lhoussaine Zarayby,&nbsp;Ibrahim Sbai El-Otmani","doi":"10.1016/j.vascn.2023.107294","DOIUrl":"10.1016/j.vascn.2023.107294","url":null,"abstract":"<div><p>Benzodiazepines are one of the most widely used classes of drugs around the world. They are medically used in different therapeutic areas including insomnia, anxiety, epilepsy, and anesthesia. Unfortunately, these drugs are very widespread in the illicit market for recreational purposes and cause drug dependence, traffic accidents, and criminality. Furthermore, benzodiazepine misuse leads to acute poisoning cases that often end up in hospital emergency rooms. Therefore, it is crucial for hospitals to possess straightforward and efficient bioanalytical techniques that enable the swift detection of benzodiazepines in biological samples. This review provides a general overview of the different bioanalytical techniques used for the detection and quantification of benzodiazepines in biological samples and emphasizes their suitability for emergency toxicological analyzes.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9865102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of three different 99mTc-based mock-venom agents for lymphoscintigraphy studies in preclinical models of peripheral snakebite envenomation","authors":"Nidhi Tiwari ,&nbsp;Abhinav Jaimini ,&nbsp;Gaurav Kumar Jain ,&nbsp;Geeta Aggarwal ,&nbsp;Gaurav Mittal","doi":"10.1016/j.vascn.2023.107280","DOIUrl":"https://doi.org/10.1016/j.vascn.2023.107280","url":null,"abstract":"<div><p>Snakebite envenomation is one of the major public health concerns across many countries; with the WHO designating it as a ‘priority neglected tropical disease’ and stressing for a need to develop novel therapeutic strategies to reduce death and disability rate by end of 2030. Since a major component of venom; the high molecular weight (HMw) toxins enter the bloodstream through lymphatic system, research is focusing on modulating the lymphatic flow rate after topical application of suitable drug candidates. Present study compared the suitability of three radiopharmaceutical agents, namely ^99mTc-Sulfur colloid (SC), ^99mTc-Phytate (Phy) and ^99mTc-Human serum albumin (HSA), to be used as mock-venom agent in studying modulation in lymphatic flow rate in preclinical models of peripheral snakebite envenomation using lymphoscintigraphy studies. The study was performed in 72 Sprague Dawley rats; divided into six groups of 12 rats each. Control groups were given intradermal injection (1.29–1.48 MBq in 100 μl normal saline) of either ^99mTc-Phy/ ^99mTc-SC/ ^99mTc-HSA into the tail as ‘mock-venom’. In respective test groups, commercially available topical formulation (Anobliss® Cream) containing Nifedipine (Nif; 0.3% <em>w</em>/w) and Lidocaine (Lid; 1.5% w/w) was applied topically over the animals' lower body (tail and hind limbs) immediately within 20s of administering intradermal injection of the radiopharmaceutical. Any modulation in lymph transit time from periphery to systemic circulation was assessed using lymphoscintigraphy by taking dynamic gamma-scintigraphy images of 60s each till 1 h post-injection of the test radiopharmaceuticals. Significant difference in movement of the three radiopharmaceuticals was noted in terms of their lymphatic movement. ^99mTc-Phy did not show significant travel through the lymphatics and the liver was faintly visualized in control as well as test intervention groups. In case of ^99mTc-SC, significant changes in movement of the radiotracer after topical application of Nif/Lid in the test intervention groups were clearly noted in comparison to control (<em>P</em> &lt; 0.05). Multiple numbers of lymph nodes (LNs) could be clearly visualized in control (5 ± 1 LNs) and test intervention groups (3 ± 1 LNs). Liver uptake was more prominent in control animals and it reduced significantly in test intervention groups. On the other hand, ^99mTc-HSA showed lesser number of lymph nodes and higher accumulation in liver as compared to ^99mTc-SC, suggesting very fast movement of this radiopharmaceutical. Results indicates that ^99mTc-SC could be used as a suitable agent to mimic lymphatic transit behavior of HMw toxin components of snake venom and could therefore be used as a model in studying the effect of any test pharmacological intervention in modulating lymphatic transit rate. Additional advantage could be a si","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50197553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HS-GC-FID method for quantification of HFA-152a in cell culture media, and plasma from a range of species and regulatory compliant validations","authors":"Philip J. Kuehl ,&nbsp;Stuart Corr ,&nbsp;Jabari Farrar ,&nbsp;Jacob D. McDonald ,&nbsp;Tim Wermer ,&nbsp;Derek Weber ,&nbsp;Chet Leach","doi":"10.1016/j.vascn.2023.107271","DOIUrl":"10.1016/j.vascn.2023.107271","url":null,"abstract":"<div><h3>Introduction</h3><p>1,1-Difluoroethane (HFA-152a) is being developed as an alternative propellant in pressurized metered dose inhalers (pMDIs). As a part of the regulatory development pathway, pharmacology, toxicology and clinical studies have been conducted with inhaled HFA-152a. These studies require fit for purpose regulatory compliant (GxP validated) methods for quantification of HFA-152a from blood.</p></div><div><h3>Methods</h3><p>As HFA-152a is a gas at standard temperature and pressure, novel methods were developed to support the analysis across the wide range of species and concentrations required for regulatory filing.</p></div><div><h3>Results</h3><p>The developed methods utilized a headspace auto sampler coupled to a gas chromatograph (GC) with flame ionization detection. Key factors in the successful method included bringing together fit for purpose approaches to the head space vials, volume of matrix (blood), detection range required for species/study objective, handling / transfer of blood into head space vials and the stability/storage required for the analysis of the samples. The species-specific assays were fully validated under regulatory (GLP) conditions for mouse, rat, rabbit, canine and human and non-regulatory (non GLP) validations for guinea pig and cell culture media.</p></div><div><h3>Discussion</h3><p>Overall the novel approach of head space analysis of whole blood allowed for the development and validation of assays used to generate the toxicokinetic data that supported clinical testing of HFA-152a as a new pMDI propellant.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization","authors":"Elham Ataei Alizadeh,&nbsp;Karin Graf,&nbsp;Jessica Schiwon,&nbsp;Thomas Trautmann,&nbsp;Florian Krause,&nbsp;Werner Mayer,&nbsp;Katrin Christ,&nbsp;Eric Martel,&nbsp;Brian D. Guth,&nbsp;Michael Markert","doi":"10.1016/j.vascn.2023.107279","DOIUrl":"10.1016/j.vascn.2023.107279","url":null,"abstract":"<div><p>Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the years to improve both the data quality and the well being of our animal subjects. Of particular interest for us has been the use of telemetry-based data acquisition for conducting studies on cardiovascular (CV) function. This includes the evolving technical aspects of the studies, as well as the development of new applications that take advantage of this technical approach.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9798252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The incidence of spontaneous arrhythmias in telemetered beagle dogs, Göttingen Minipigs and Cynomolgus non-human primates: A HESI consortium retrospective analysis","authors":"Emmanuel Boulay ,&nbsp;Loïs S. Miraucourt ,&nbsp;Michael K. Pugsley ,&nbsp;Matthew M. Abernathy ,&nbsp;Ray Chui ,&nbsp;Jill Dalton ,&nbsp;Marjorie Demers ,&nbsp;Noel Dybdal ,&nbsp;Elissa Gazaille ,&nbsp;Andrea Greiter-Wilke ,&nbsp;Peter Hoffmann ,&nbsp;Hai Huang ,&nbsp;Carrie LaDuke ,&nbsp;Kevin Norton ,&nbsp;Jennifer B. Pierson ,&nbsp;Isabelle Reeves ,&nbsp;Brian Roche ,&nbsp;Eric I. Rossman ,&nbsp;Albert E. Schultze ,&nbsp;Hai-Ming Tang ,&nbsp;Simon Authier","doi":"10.1016/j.vascn.2023.107266","DOIUrl":"10.1016/j.vascn.2023.107266","url":null,"abstract":"<div><h3>Introduction</h3><p>Characterization of the incidence of spontaneous arrhythmias to identify possible drug-related effects is often an important part of the analysis in safety pharmacology studies using telemetry.</p></div><div><h3>Methods</h3><p>A retrospective analysis in non-clinical species with and without telemetry transmitters was conducted. Electrocardiograms (24 h) from male and female beagle dogs (<em>n</em> = 131), Göttingen minipigs (<em>n</em> = 108) and cynomolgus non-human primates (NHP; <em>n</em> = 78) were analyzed.</p></div><div><h3>Results</h3><p>Ventricular tachycardia (VT) was observed in 3% of the dogs but was absent in minipigs and NHPs. Ventricular fibrillation (VF) was not observed in the 3 species. Ventricular premature beats (VPBs) were more frequent during daytime and atrioventricular blocks (AVBs) were more frequent at night in all species. A limited number of animals exhibited a high arrhythmia frequency and there was no correlation between animals with higher frequency of an arrhythmia type and the frequency of other arrythmias in the same animals. Clinical chemistry or hematology parameters were not different with or without telemetry devices. NHP with a transmural left ventricular pressure (LVP) catheter exhibited a greater incidence of VPBs and PJCs compared to telemetry animals without LVP.</p></div><div><h3>Discussion</h3><p>All species were similar with regards to the frequency of ventricular ectopic beats (26–46%) while the dog seemed to have more frequent junctional complexes and AVB compared to NHP and minipigs. Arrhythmia screening may be considered during pre-study evaluations, to exclude animals with abnormally high arrhythmia incidence.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9494246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}