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Transcriptome and open chromatin analysis reveals the process of myocardial cell development and key pathogenic target proteins in Long QT syndrome type 7
ObjectiveLong QT syndrome type 7 (Andersen–Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia,...
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Obesity Potentiates the Risk of Drug-Induced Long QT Syndrome - Preliminary Evidence from WNIN/Ob Spontaneously Obese Rat
Drug-induced long QT syndrome (DI-LQTS) is fatal and known to have a higher incidence in women rather than in men. Multiple risk factors potentiate...
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Status of Safety Pharmacology and Present Guidelines
This chapter describes the development from General Pharmacology to Safety Pharmacology. The development of the different ICH guidelines is discussed...
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Absence of QTc prolongation in a thorough QT study with imeglimin, a first in class oral agent for type 2 diabetes mellitus
PurposeImeglimin is the first in a new class of oral antidiabetic agents, the glimins, currently in development to improve glycemic control in...
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Plasma potassium concentration and cardiac repolarisation markers, Tpeak–Tend and Tpeak–Tend/QT, during and after exercise in healthy participants and in end-stage renal disease
PurposeThe cardiac T-wave peak-to-end interval (T pe ) is thought to reflect dispersion in ventricular repolarisation, with abnormalities in T pe ...
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Analysis of clinical characteristics and automatic monitoring of drug-induced arrhythmias in 167,546 inpatients
ObjectiveThe purpose of this study was to analyze the occurrence characteristics, clinical manifestations, medication distribution, and incidence of...
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Kv11.1 (hERG1) Channels and Cardiac Arrhythmia
The rapid delayed rectifier K+ current (IKr) is one of several outward currents that mediate repolarization of cardiac action potentials in humans...
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Impact of Phase 1 study design on estimation of QT interval prolongation risk using exposure–response analysis
The International Council for Harmonisation (ICH) guidelines have been revised allowing for modeling of concentration-QT (C-QT) data from Phase I...
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QTc Prolongation in COVID-19 Patients Using Chloroquine
Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect....
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Association Between Vomiting and QT Hysteresis: Data from a TQT Study with the Endothelin A Receptor Antagonist Clazosentan
This study investigated the potential QT liability of the selective endothelin-1 A receptor antagonist clazosentan at a therapeutic (20 mg/h) and...
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Electrophysiological Profile of Different Antiviral Therapies in a Rabbit Whole-Heart Model
Antiviral therapies for treatment of COVID-19 may be associated with significant proarrhythmic potential. In the present study, the potential...
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PKPD and cardiac single cell modeling of a DDI study with a CYP3A4 substrate and itraconazole to quantify the effects on QT interval duration
Plasma drug concentration and electrocardiogram (ECG) data from a drug–drug interaction (DDI) study employing the metabolic inhibitor itraconazole...
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Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study
Nifekalant hydrochloride is a class III antiarrhythmic agent which could increase the duration of the action potential and the effective refractory...
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Doses Evaluated in Clinical Pharmacology Studies Investigating the Effect of Intrinsic and Extrinsic Factors on PK and Safety: Case Examples from Approved Drug Development Programs
Dose selection for investigations of intrinsic and extrinsic factors of pharmacokinetic variability as well as safety is a challenging question in...
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Validation of Corrected and Dispersed QT as Predictors of Adverse Outcomes in Acute Cardiotoxicities
Acute cardiovascular poisoning is a major cause of adverse outcomes in poisoning emergencies. The prognostic validity of corrected QT (QTc) and...
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Concomitant Treatment with Proton Pump Inhibitors and Cephalosporins Does Not Enhance QT-Associated Proarrhythmia in Isolated Rabbit Hearts
Recent results from data mining analyses and reports of adverse drug events suggest a QT-prolonging drug–drug interaction resulting from the...
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The grapefruit polyphenol naringenin inhibits multiple cardiac ion channels
Drinking fresh grapefruit juice is associated with a significant prolongation of the QT segment on the electrocardiogram (ECG) in healthy volunteers....
