Aim: To learn the electrophysiological interference of levofloxacin (LVFX) to heart in guinea pig.
Methods: High, moderate and low doses of LVFX were given to the anesthetic guinea pig via i.p., and QT interval span and corrected QT-interval span in the II leading lines of ECG were recorded and analyzed from 5 min to 360 min after the drug administration. Single ventricular myocytes were obtained and impacted by LVFX solution of different concentrations. Then delayed rectifier potassium currents (I(K)) on single cells were recorded with whole-cell patch clamp technique, and compared with control group(without impact of LVFX).
Results: (1) After the administration of LVFX, at the dose of 200 mg/kg. QT-interval span was significantly elongated, and the increasing rate is 19.38% +/- 3.15% (P < 0.05). While at the relatively lower doses of 50 mg/kg and 100 mg/kg, the elongation is of low/no significance (P > 0.05). (2) LVFX inhibited I(K) dose-dependently and time-dependently.
Conclusion: LVFX might prolong the QT-interval span by the mechanism of inhibiting I(K), which implies a potential risk in clinical application.
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J Pharmacol Toxicol Methods
December 2024
Charles River Laboratories, Mattawan, United States.
Nonclinical QTc studies can augment clinical QTc assessments in regulatory submissions provided they are of sufficient quality and sensitivity. Both the statistical performance and species translation play a role in determining the sensitivity of the model. The current analyses examine the effects of dofetilide or vehicle on the QT interval in nonhuman primate (NHP; n = 16) using a one-step estimated marginal means method where both treatment and animal ID are used in regression models to avoid a separate rate correction step, in comparison to other commonly utilized methods.
View Article and Find Full Text PDFJ Am Heart Assoc
April 2024
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation Oklahoma City OK USA.
Background: Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) is a critical glycolytic regulator responsible for upregulation of glycolysis in response to insulin and adrenergic signaling. PFKFB2, the cardiac isoform of PFK-2, is degraded in the heart in the absence of insulin signaling, contributing to diabetes-induced cardiac metabolic inflexibility. However, previous studies have not examined how the loss of PFKFB2 affects global cardiac metabolism and function.
View Article and Find Full Text PDFJ Womens Health (Larchmt)
July 2021
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Clin Pharmacol Drug Dev
May 2021
Novo Nordisk Inc., Plainsboro, New Jersey, USA.
Macimorelin is an orally active growth hormone secretagogue indicated for the diagnosis of adult growth hormone deficiency. The primary objective of this study was to evaluate the effect of macimorelin on the baseline and placebo-corrected mean QT interval using Fridericia's formula (ΔΔQTcF). Secondary objectives were to determine QTcF for moxifloxacin; evaluate the effects of macimorelin on other cardiac intervals (PR, QRS, RR), heart rate, and electrocardiogram morphology parameters; characterize pharmacokinetics; and assess safety of macimorelin.
View Article and Find Full Text PDFIntern Med J
June 2019
First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.
Background: Clinical variables that predict long-term mortality and recurrence of Takotsubo syndrome (TTS) are not completely understood as the role of acquired corrected QT interval (QTc) prolongation.
Aim: To detect the prevalence of QTc interval prolongation in patients with TTS and to evaluate its long-term prognostic impact.
Methods: QTc intervals were analysed in 105 patients presenting with symptoms of TTS.
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