Journal of pharmacological and toxicological methods最新文献

{"title":"Optimization strategy for modeling sick sinus syndrome in rats: Balancing effect and animal care","authors":"Liming He ,&nbsp;Xinxin Shi ,&nbsp;Yucheng Wang ,&nbsp;Shuwei Huang","doi":"10.1016/j.vascn.2025.108399","DOIUrl":"10.1016/j.vascn.2025.108399","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to validate the feasibility of establishing a sick sinus syndrome (SSS) rat model by injecting 3 % sodium hydroxide (NaOH) into the jugular vein at a rate of 0.01 mL/s, and to assess reductions in animal mortality and vascular injury.</div></div><div><h3>Results</h3><div>Compared with the conventional 10 % NaOH method, the modified 3 % NaOH approach yielded a significantly higher modeling success rate (78 % vs. 44 %), substantially lower mortality (15 % vs. 48 %), and reduced jugular vein injury. Electrophysiological evaluations demonstrated a time-dependent decrease in post-modeling heart rate (HR), characterized by widened P-waves and prolonged PR intervals. Additionally, heart rate variability (HRV) analysis revealed a notable increase in the standard deviation of normal-to-normal intervals (SDNN) 2 weeks post-modeling. Histopathological analysis (HE staining) indicated more pronounced necrosis and fibrosis in sinus node P-cells, accompanied by elevated levels of hydroxyproline (HYP) and transforming growth factor β1 (TGF-β1). Furthermore, assessments of pacing-related ion channels showed downregulated transcription and expression of hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and reduced <em>SCN5A</em> transcription, aligning with observed electrophysiological abnormalities.</div></div><div><h3>Conclusion</h3><div>The modified 3 % NaOH method effectively establishes an SSS rat model, offering advantages in simplicity, cost-efficiency, and animal welfare. This model provides a practical platform for fundamental SSS research, especially in resource-limited laboratories.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"136 ","pages":"Article 108399"},"PeriodicalIF":1.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155724","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":"LC–MS/MS-based simultaneous quantification of chlorthalidone and cilnidipine in rat plasma: Pharmacokinetic evaluation, green analytical assessment, and DoE-driven optimization","authors":"Sravanthi Gandu,&nbsp;Kumaraswamy Gandla,&nbsp;Lalitha Repudi","doi":"10.1016/j.vascn.2025.108400","DOIUrl":"10.1016/j.vascn.2025.108400","url":null,"abstract":"<div><div>A highly sensitive and reproducible liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was systematically developed and optimized using a Quality by Design (QbD) framework for the simultaneous quantification of chlorthalidone and cilnidipine in rat plasma. Critical method variables—organic phase composition, flow rate, and mobile phase pH—were identified through risk assessment and subsequently optimized via Box–Behnken Design to ensure analytical robustness. Optimal chromatographic conditions comprised 20 % organic content, a flow rate of 1.0 mL/min, and a mobile phase pH of 3.0, facilitating efficient resolution of both analytes. Detection was achieved in positive electrospray ionization mode using multiple reaction monitoring, with transitions of <em>m</em>/<em>z</em> 339.8909 → 85.0951 for chlorthalidone, <em>m</em>/<em>z</em> 493.5237 → 300.1587 for cilnidipine, and m/z 515.6423 → 342.6158 for telmisartan, employed as the internal standard. Method validation, performed in accordance with European Medicines Agency (EMA) guidelines, demonstrated excellent linearity (r² &gt; 0.998), accuracy, and precision, with coefficient of variation consistently &lt;10 %. The method exhibited strong analyte stability and was successfully applied to the pharmacokinetic evaluation of both drugs in Wistar rats. This DoE-optimized LC–MS/MS platform offers a selective, reliable, and environmentally conscious analytical solution for the preclinical assessment of chlorthalidone and cilnidipine.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"136 ","pages":"Article 108400"},"PeriodicalIF":1.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182447","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":"Exploratory safety investigations in normal, freely moving Göttingen Minipigs using telemetry: Pharmacological validation","authors":"Julie Jacobsen,&nbsp;Berit Ø. Christoffersen","doi":"10.1016/j.vascn.2025.108395","DOIUrl":"10.1016/j.vascn.2025.108395","url":null,"abstract":"<div><h3>Introduction</h3><div>Adverse cardiovascular (CV) effects is a major cause of drug attrition. Early assessment of CV risk for new drug candidates may be warranted for early de-risking of the further development. Predictive animal models and a careful study design are needed for decision-making. The aim of this study was to characterise the CV effects of three cardiometabolic compounds with known CV effects in humans – the GLP-1 receptor agonist liraglutide, the melanocortin receptor 4 agonist (MC4-RA) LY2112688 and urocortin-2 (UCN2) - in Göttingen Minipigs to evaluate the predictability of this model.</div></div><div><h3>Materials and methods</h3><div>Female Göttingen Minipigs with telemetry implants (<em>n</em> = 6–8) were used in 3 consecutive cross-over studies looking at CV effects of liraglutide, LY2112688 and UCN2. Main endpoints were: Mean arterial blood pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR), in addition to activity and body temperature.</div></div><div><h3>Results</h3><div>Liraglutide at the highest dose level of 3 nmol/kg (Day 7) induced a significant increase in 24 h HR (<em>p</em> &lt; 0.01) compared to vehicle. No significant differences in MAP, SBP or DBP were observed. The MC4-RA LY2112688 at a dose level of 0.1–0.15 mg/kg (Day 4) gave rise to significant increases in all of 24 h HR (<em>p</em> &lt; 0.05), MAP (<em>p</em> &lt; 0.01), SBP (p &lt; 0.01) and DBP (p &lt; 0.05) compared to vehicle. UCN2 infusion resulted in a significant increase in HR (<em>p</em> &lt; 0.05) and a significant decrease in SBP (p &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>The study highlights different CV study designs in Göttingen Minipigs and show that this model qualitatively reproduced the CV effects observed in humans following treatment with the three test compounds. These data support the minipig as a translational preclinical model for exploratory safety evaluations, although the magnitude of the changes may not translate completely between species.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"136 ","pages":"Article 108395"},"PeriodicalIF":1.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042691","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":"Introducing the Sinclair Nanopig™ model: Preliminary genomic, proteomic, and hepatic CYP450 characterization for (bio)pharmaceutical safety assessment","authors":"Yafei Chen ,&nbsp;Nathan Bivens ,&nbsp;Hong An ,&nbsp;Brian Mooney ,&nbsp;Thao Nguyen ,&nbsp;Lyndon Coghill ,&nbsp;Jennifer Horkman ,&nbsp;Lois Haupt ,&nbsp;Melissa Evans ,&nbsp;Rebecca Campbell ,&nbsp;Wendell Davis","doi":"10.1016/j.vascn.2025.108394","DOIUrl":"10.1016/j.vascn.2025.108394","url":null,"abstract":"<div><div>The Nanopig™ model is an emerging non-rodent platform for (bio)pharmaceutical safety assessment, with potential advantages for translational research. Here, we report initial characterization results using whole genome sequencing (WGS) and tissue-based proteomics, focusing on drug metabolism and immune system relevance. WGS produced a high-quality Nanopig™ genome assembly (2.8–2.9 Gb), with &gt;98 % alignment to the Duroc pig reference genome, and identified key metabolic and immune-related genes, including 47 cytochrome P450 (CYP450) genes with high homology to human CYP450 families. Proteomic profiling of 15 pharmaceutically relevant tissues revealed human orthologous drug metabolism enzymes and transporters (DMETs), as well as immune-related proteins, indicating similarities to human CYP450 enzyme abundance and tissue distribution. Functional evaluation of hepatic CYP450 activity yielded kinetic parameters (K_m, V_max) in the range observed in humans and beagle dogs. These early findings represent a foundational multi-omics dataset for the Nanopig™, suggesting its future use as a translational model in preclinical safety assessment. This work provides an early framework for species selection strategies and model optimization, with the long-term goal of reducing reliance on traditional non-rodent species in drug development.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"136 ","pages":"Article 108394"},"PeriodicalIF":1.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020812","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":"PolyCheck: A hybrid model for predicting polypharmacy-induced adverse drug reactions in tuberculosis treatment using heterogenous drug-target-ADR networks","authors":"Ahmad Tamim Ghafari ,&nbsp;Yuslina Zakaria ,&nbsp;Mizaton Hazizul Hasan ,&nbsp;Abu Bakar Abdul Majeed ,&nbsp;Qand Agha Nazari","doi":"10.1016/j.vascn.2025.108393","DOIUrl":"10.1016/j.vascn.2025.108393","url":null,"abstract":"<div><div>Polypharmacy during tuberculosis (TB) treatment, particularly in patients with comorbidities such as diabetes mellitus (DM), significantly increases the risk of adverse drug reactions (ADRs) due to complex drug–drug interactions (DDIs). Existing computational methods primarily focus on pairwise drug interactions, often failing to capture the multifactorial nature of ADRs in polypharmacy contexts. To address this gap, we developed PolyCheck, a hybrid predictive model that integrates network-based and rule-based methods to identify potential ADRs arising from multi-drug regimens. We constructed a heterogeneous Drug–Target–ADR interaction network comprising first-line anti-TB and antidiabetic drugs, their targets, and associated ADRs. The Random Walk with Restart (RWR) algorithm was employed to rank ADR nodes, and a rule-based layer further refined predictions by incorporating the biological relevance of Drug–Target–ADR associations. Evaluation using cross-validation and case-based testing demonstrated strong predictive performance, with accuracy, precision, recall, F1-score, and AUPRC values of 0.70, 0.74, 0.92, 0.81, and 0.74, respectively. PolyCheck offers a scalable and interpretable approach for predicting ADRs in complex treatment regimens and can support safer, individualized TB therapy in patients with comorbid conditions.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"136 ","pages":"Article 108393"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994901","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":"Investigation of in vitro IKr/hERG assays under physiological temperature conditions using the semi-automated patch-clamp system QPatch compact with temperature control system","authors":"Kazuya Tsurudome,&nbsp;Hironori Ohshiro,&nbsp;Taku Izumi","doi":"10.1016/j.vascn.2025.107814","DOIUrl":"10.1016/j.vascn.2025.107814","url":null,"abstract":"<div><div>Cardiac ion channel activity is crucial for generating cardiac action potentials with proper timing and duration. Drug-induced impairment of these ion channels can cause abnormal cardiac activity, including QT interval prolongation, ventricular arrhythmia, and, in the most severe cases, sudden death. These adverse effects are among the leading reasons for drug withdrawal from the market or the denial of regulatory approval for new therapeutic candidates. The ICH E14/S7B Q&amp;A released in August 2022 provided recommended conditions for best practices for in vitro assay of IKr/hERG to maintain reproducibility and consistency in evaluations. These recommendations include testing under physiological temperature conditions, as well as considering factors such as voltage protocols. In this study, we have investigated whole-cell patch-clamp measurements of hERG currents under physiological temperature conditions (36–37 °C) using the semi-automated patch-clamp system QPatch compact using the recommended best practices. Whole-cell patch-clamp recordings in hERG channel-expressing cells were performed using the QPatch Compact automated patch-clamp system with a temperature control system and the voltage protocol recommended by the CiPA project. Compared to room temperature conditions, the rise time of the hERG current was shorter and its amplitude larger under physiological temperature conditions. The tail current decay rate was also slower. The overall duration of the current was prolonged. These findings imply that temperature influences the dynamics of hERG channels, providing a more accurate reproduction of their physiological function. Furthermore, when testing the temperature-dependent effects of erythromycin, the current inhibition rate at the highest applied concentration of 1000 μM was around 50 % under room temperature conditions (25 °C). In contrast, under physiological temperature conditions, the IC50 was approximately 60 μM, and a nearly complete blockade of hERG currents was achieved at 1000 μM. This result confirms that the inhibitory effect of erythromycin is more pronounced under physiological temperature conditions. Additionally, we have tested other reference compounds, such as dofetilide, ondansetron, and moxifloxacin, to assess their temperature sensitivity. These insights are expected to improve our understanding of the influence of temperature on drug effects and enhance the reliability of testing protocols in accordance with ICH guidelines.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"135 ","pages":"Article 107814"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094844","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":"Compound A, a novel dual mu and kappa opioid receptor agonist that exerts potent an analgesic effect comparable to oxycodone, showed no reinforcing effect in monkeys","authors":"Yukiko Orita ,&nbsp;Atsushi Nakamura ,&nbsp;Yuki Azuma ,&nbsp;Kana Yasufuku ,&nbsp;Erika Kasai ,&nbsp;Tohko Arai","doi":"10.1016/j.vascn.2025.107800","DOIUrl":"10.1016/j.vascn.2025.107800","url":null,"abstract":"<div><div>Opioids (opioid mu receptor [MOR] agonists) are one of the most powerful analgesics and are widely used around the world, however, the rapid increase in the number of deaths due to drug abuse and overdose have become a major social problem. One of the causes of opioid-mediated abuse is known to be an increase of dopamine release in nucleus accumbens (NAc) via MOR activation in brain, and this effect is also known to be counteracted by opioid kappa receptor (KOR) activation expressed in NAc. We, therefore, hypothesized that a MOR/KOR dual agonist would be able to avoid the risk of abuse and psychological dependence while maintaining a strong analgesic effect. In this study, we evaluated the analgesic effects and reinforcing effect of Compound A, a novel MOR/KOR dual agonist (non-morphinan structure) that we created and compared with those of oxycodone. To investigate in vitro functional activity of compound A, cAMP assay was conducted. Hot-plate test (55°C) in rats (<em>n</em> = 5/dose, p.o) was performed to assess the analgesic effect. The time-course of dopamine level in NAc in rats was determined using in vivo microdialysis method (<em>n</em> = 3–8/dose, i.v.). Abuse liability was assessed by rat conditioned place preference (CPP) test (<em>n</em> = 7/dose, i.v.) and monkey intravenous self-administration study under a fixed-ratio 30 schedule of reinforcement (<em>n</em> = 4/dose, i.v.). In vitro profile, Compound A exhibited MOR and KOR agonism. Compound A exhibited dose-dependent analgesic effect, with a maximum response comparable to or greater than that of oxycodone. Compound A introduced less level dopamine release in rat NAc compared to oxycodone and no increase of CPP score at the analgesic dose in rats. In monkeys, Compound A did not show any reinforcing properties over a wide dose range covering the expected clinical pharmacological exposure, whereas oxycodone showed a strong reinforcing effect. MOR/KOR dual agonists may be able to overcome the risk of abuse and psychological dependence of traditional opioids while maintaining a potent analgesic effect comparable to them, which would contribute to one solution of current opioid crisis.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"135 ","pages":"Article 107800"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095109","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":"Historical control data of nonclinical nerve conduction parameters in nonhuman primates","authors":"Andrew R. Brown,&nbsp;Nataliya Sadekova,&nbsp;Kevin Norton,&nbsp;Mark C. Freke","doi":"10.1016/j.vascn.2025.107837","DOIUrl":"10.1016/j.vascn.2025.107837","url":null,"abstract":"<div><div>Damage to the peripheral nervous system (neuropathy) can develop as a side effect of certain classes of therapeutic compounds or from toxin exposure, disease, and traumatic injury. Given the clinical significance of neuropathy, it can be critical to characterize nerve function during the nonclinical safety assessment of certain classes of compounds. Additionally, recent characterization of dorsal root ganglion toxicity following adeno-associated viral therapies stresses the need for in vivo assessment of potential nerve damage on these studies. Nerve conduction evaluations provide an electrophysiological approach to assess nerve function, are a sensitive and valid index of induced neuropathies, can be conducted at multiple time points throughout the treatment period, and provide quantitative data for evaluation. Here, we present a dataset of normative values for nerve conduction parameters in nonhuman primates generated by a retrospective analysis of historical control data from 16 Charles River studies comprising 491 young adult male and female cynomolgus monkeys, approximately 1.5–5 years of age. Nerve panels consisted of distal hindlimb peroneal motor and sural sensory nerves, a proximal mixed segment of the hindlimb sciatic nerve, and distal forelimb median sensory nerve. Evaluation parameters included response onset latency, nerve conduction velocity (NCV), and amplitude, as appropriate, for each nerve with animal sex and country of origin as independent variables. NCV values for each nerve were largely consistent between studies while response amplitudes exhibited more variability, indicating the importance of establishing prestudy baselines and incorporating a concurrent control group for postdose assessments. No sex differences were observed for NCV or amplitude parameters, indicating that sexes can be pooled to increase sample size and experimental power while potentially reducing the total animals required for each study. An animal country of origin effect on response parameters was observed which related, in part, to differences in animal size. Collectively, the dataset provides a comprehensive overview of control values for young adult cynomolgus monkeys to assess the sensitivity of the technique to properly characterize a potential effect. It is considered suitable to aid in the interpretation of potential neuropathy for nerve conduction evaluations used in nonclinical toxicology studies.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"135 ","pages":"Article 107837"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095356","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":"Emerging neurology safety biomarkers for advanced modality therapeutic-associated neurotoxicity in nonhuman primates","authors":"Catherine F. Ruff,&nbsp;Tanja S. Zabka,&nbsp;Tien Nguyen,&nbsp;Donna Lee","doi":"10.1016/j.vascn.2025.107838","DOIUrl":"10.1016/j.vascn.2025.107838","url":null,"abstract":"<div><div>There have been exciting advances in basic neuroscience research, yet the approval rate of novel therapeutics for neurodegenerative indications is low. In addition to poor efficacy, previously unidentified safety concerns in clinical trials are a major contributor to neurology drug attrition. Although there are regulatory-mandated safety assessments of the central nervous system in nonclinical studies, these are limited to neurofunctional tests, which are adequate for detecting overtly neurotoxic-mediated deficits, but more sensitive, specific, and quantitative methods are needed to advance the safety profiling of drug candidates early in nonclinical studies. Fluid-based biomarkers have emerged as a potential tool for improving neurotoxicity assessment, especially in life, across species. Here, we evaluated a subset of neurology biomarkers in a nonclinical toxicity study in nonhuman primates administered a single intrathecal dose of an advanced modality therapeutic molecule over an 8-week observation period. We show dose-dependent and time-dependent increases in total Tau, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1, and to a lesser extent neurofilament light (NfL) in the cerebrospinal fluid, but less compelling responses in plasma. Elevations in these biomarkers correlated with even minor microscopic evidence of neuronal necrosis, yet clinical observations were not identified on neurofunctional tests. These results demonstrate that Tau, UCH-L1, and NfL are sensitive, specific, and quantitative biomarkers of advanced modality therapeutic-associated neurotoxicity early in nonclinical studies. Furthermore, these biomarkers have the potential to improve drug candidate screening for neurologic indications and create a therapeutic index for forward translation into the clinic for these potentially life-altering drugs.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"135 ","pages":"Article 107838"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095357","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":"Advancements in cardiovascular data analysis: PAROT - A novel GLP-compliant application for efficient telemetry and ECG data visualization and reporting","authors":"Corey R. Petrella","doi":"10.1016/j.vascn.2025.107773","DOIUrl":"10.1016/j.vascn.2025.107773","url":null,"abstract":"<div><div>Some of the challenges associated with the conduct of cardiovascular (CV) telemetry studies include the analysis, review, and management of large datasets that may be collected across different species (e.g., rat, dog, or NHP) using various study designs (e.g., cross-over or parallel). Many labs consequently face limitations such as lack of flexibility, control, and ease of GLP-compliant upgrades using either internal or off-the-shelf applications. In response to the ICH E14/S7B Q&amp;As and best practice recommendations along with internal demand for efficient data reporting and visualization tools for CV telemetry and surface lead ECG data analysis, we have developed a novel GLP-compliant application termed Ponemah Analysis and Reporting Output Tool (PAROT). The PAROT application is a web-based platform designed to address limitations in our existing analysis tools, enhancing CV data analysis by enabling users to analyze, visualize, and generate files to allow for statistical analysis and SEND reporting. PAROT integrates with other platforms such as Ponemah for data acquisition/analysis and SAS for statistical analysis (e.g., ANOVA) and reporting. This has led to efficiency gains in data review, interpretation, reporting and informed decision making. The purpose of this abstract is to highlight the development and application of PAROT while demonstrating some of its features using real-world exemplary data that facilitate data review consistent with ICH S7B Q&amp;As. These features include individual animal and group mean time course plots for all CV parameters, scatter plots of QT/QTc vs. HR/RR to evaluate heart rate correction methods, and statistical outputs showing least significant difference (LSD) and root mean square error (RMSE) values to demonstrate study sensitivity. Finally, the summary data can be exported to generate a file consistent with SEND. While this application is specific for internal use, it serves as a model for harmonizing data integrity, analysis, and compliance in CV studies. In summary, the PAROT application represents an enhancement in CV data review and visualization, while integrating current updates in regulatory guidance and enabling users to utilize their data effectively in drug safety and development.</div></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"135 ","pages":"Article 107773"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095370","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}