The impact of drug-induced QT interval prolongation on drug discovery and developmentBernard Fermini
Pfizer Global Research and Development, Eastern Point Road MS 4083, Groton, Connecticut 06340, USA
Nat Rev Drug Discov 2:439-47. 2003
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Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetineAnthony A Fossa
Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340, USA Electronic address
Toxicol Appl Pharmacol 264:343-50. 2012
..safety compared to acute NRI treatment...
- The use of beat-to-beat electrocardiogram analysis to distinguish QT/QTc interval changes caused by moxifloxacin from those caused by vardenafil
A A Fossa
iCardiac Technologies, Rochester, New York, USA
Clin Pharmacol Ther 90:449-54. 2011
..This study demonstrated that newer methods of electrocardiogram (ECG) analysis can differentiate changes in the QT interval to improve identification of proarrhythmia risk...
- Assessing QT prolongation and electrocardiography restitution using a beat-to-beat method
Anthony A Fossa
iCardiac Technologies, Rochester, New York 14618, USA
Cardiol J 17:230-43. 2010
..This analysis potentially provides an additional means to quantify cardiac stress or arrhythmia vulnerability as the heart works more in relationship to each rest cycle...
- Assessing QT prolongation in conscious dogs: validation of a beat-to-beat method
Anthony A Fossa
iCardiac Technologies, Inc, 150 Allens Creek Road, Rochester, NY 14618, United States
Pharmacol Ther 119:133-40. 2008
..However, some caveats based on observations may need to be considered due to inherent differences in QT intervals and sinus arrhythmia between canines and humans...
The impact of varying autonomic states on the dynamic beat-to-beat QT-RR and QT-TQ interval relationshipsA A Fossa
Cardiovascular Safety, iCardiac Technologies Inc, Rochester, NY 14618, USA
Br J Pharmacol 154:1508-15. 2008
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- Assessing QT prolongation in conscious dogs: validation of a beat-to-beat method
Anthony A Fossa
iCardiac Technologies, Inc, 150 Allens Creek Road, Rochester, NY 14618, United States
Pharmacol Ther 118:231-8. 2008
..However, some caveats based on observations may need to be considered due to inherent differences in QT intervals and sinus arrhythmia between canines and humans...
- Statistical analysis of QT interval as a function of changes in RR interval in the conscious dog
D Raunig
Department of General Pharmacology, Pfizer Inc. Global Research and Development, Groton, CT 06340, USA
J Pharmacol Toxicol Methods 46:1-11. 2001
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- The relationship of clinical QT prolongation to outcome in the conscious dog using a beat-to-beat QT-RR interval assessment
Anthony A Fossa
Pfizer Global Research and Development, Eastern Point Road, Building 118, MS 4036, Groton, CT 06340, USA
J Pharmacol Exp Ther 302:828-33. 2002
..Inspection of the beat-to-beat QT-RR interval relationship in an individual animal can increase the sensitivity for more accurate clinical prediction...
- QT prolongation modifies dynamic restitution and hysteresis of the beat-to-beat QT-TQ interval relationship during normal sinus rhythm under varying states of repolarization
Anthony A Fossa
Pfizer Global Research and Development, Groton, CT 06340, USA
J Pharmacol Exp Ther 316:498-506. 2006
..Thus, dynamic beat-to-beat measurements of restitution could lead to clinically applicable ECG obtained biomarkers for assessment of changes associated with arrhythmogenic risk...
- Dynamic beat-to-beat modeling of the QT-RR interval relationship: analysis of QT prolongation during alterations of autonomic state versus human ether a-go-go-related gene inhibition
Anthony A Fossa
Pfizer Global Research and Development, Eastern Point Rd, Bldg 118, MS 4036, Groton, CT 06340, USA
J Pharmacol Exp Ther 312:1-11. 2005
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- Points to consider emerging from a mini-workshop on cardiac safety: assessing torsades de pointes liability
Alan Bass
Investigational and Regulatory Safety Pharmacology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033 0539, USA
J Pharmacol Toxicol Methods 56:91-4. 2007
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- Azithromycin/chloroquine combination does not increase cardiac instability despite an increase in monophasic action potential duration in the anesthetized guinea pig
Anthony A Fossa
Pfizer Global Research and Development, Department of Translational and Molecular Medicine, Groton, Connecticut 06340, USA
Am J Trop Med Hyg 77:929-38. 2007
..Azithromycin alone and in combination with chloroquine showed no increase in alternans beyond vehicle baseline responses indicating no additional arrhythmia liability...
- Differentiation of arrhythmia risk of the antibacterials moxifloxacin, erythromycin, and telithromycin based on analysis of monophasic action potential duration alternans and cardiac instability
Todd Wisialowski
Pfizer Global Research and Development, Eastern Point Rd, Building 274, Groton, CT 06340, USA
J Pharmacol Exp Ther 318:352-9. 2006
..9 microM). The relative risk at therapeutic concentrations is erythromycin>moxifloxacin>telithromycin and appears to be consistent with clinical observations of torsade de pointes in patients...
- Differential effect of HERG blocking agents on cardiac electrical alternans in the guinea pig
Anthony A Fossa
Pfizer Global Research and Development, Eastern Point Rd, Bldg 118, MS 4036 Groton, CT 06340, USA
Eur J Pharmacol 486:209-21. 2004
..The magnitude of effect on rate-dependent alternans may allow the differentiation of proarrhythmia and non-arrhythmic HERG blockers at clinically relevant concentrations...
- Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol
Anthony A Fossa
Pfizer Global Research and Development, Groton, Connecticut 06340, USA
Ann Noninvasive Electrocardiol 12:338-48. 2007
..We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm...
