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Predicting QT prolongation in humans during early drug development using hERG inhibition and an anaesthetized guinea-pig model

By X Yao, D L Anderson, S A Ross, D G Lang, B Z Desai, D C Cooper, P Wheelan, M S McIntyre, M L Bergquist, K I MacKenzie, J D Becherer and M A Hashim
Topics: Research Papers
Publisher: Nature Publishing Group
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Provided by: PubMed Central
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    1. (2005). Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death.
    2. (2003). Blinded test in isolated female rabbit heart reliably identifies action potential duration prolongation and proarrhythmic drugs: importance of triangulation, reverse use dependency and instability.
    3. (2006). Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias.
    4. (2005). Cardiovascular parameters in anaesthetized guinea pigs: a safety pharmacology screening model.
    5. (1996). Chronic in vivo and in vitro effects of amiodarone on guinea pig hearts.
    6. (2002). Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors.
    7. (1993). Clinical pharmacokinetics of sparfloxacin.
    8. (2004). Differential effect of HERG blocking agents on cardiac electrical alternant in the guinea pig.
    9. (2001). Drug-induced torsade de pointes: the perspectives of industry.
    10. (2005). Drugs effects on ventricular repolarization: a critical evaluation of the strengths and weaknesses of current methodologies and regulatory practices.
    11. (1995). Editorial Supervision by Pharmaceutical and Cosmetics Division, Pharmaceutical Affairs Bureau, Japanese Ministry of Health and Welfare
    12. (1999). Effect of single ascending, supratherapeutic doses of sparfloxacin on cardiac repolarization (QTc interval).
    13. (2001). Effects of 5-HT(4) receptor agonists, cisapride and mosapride citrate on electrocardiogram in anaesthetized rats and guinea-pigs and conscious cats.
    14. (1999). Effects of H1 antihistamines on animal models of QTc prolongation.
    15. (1988). Excretion and biotransformation of cisapride in dogs and humans after oral administration.
    16. (1998). Generating and influencing torsades de pointes––like polymorphic ventricular tachycardia in isolated guinea pig hearts.
    17. Hondeghem LM (2005). Refining detection of drug-induced proarrhythmia: QT interval and TRIaD.
    18. (1993). Inhibition of Na þ/Ca 2þ overload with R56865 protects against cardiac arrhythmias elicited by ouabain in vivo in guinea-pigs.
    19. (2000). Laurent A
    20. (2000). Loratadine blockade of K þ channels in human heart: comparison with terfenadine under physiological conditions.
    21. (2001). Methods of collecting and evaluating non-clinical cardiac electrophysiology data in the pharmaceutical industry: results of an international survey.
    22. (2007). Mouse models of long QT syndrome.
    23. (1998). Pharmacokinetic overview of oral second-generation H1 antihistamines.
    24. (1997). Points to consider: the assessment of the potential for QT interval prolongation by non-cardiovascular medicinal products. CPMP Predicting QT prolongation in humans XY a oet al 1455
    25. (2008). Predicting QT prolongation in humans XY a oet al 1456
    26. (2005). Prediction of the risk of torsade de pointes using the model of isolated canine Purkinje fibres.
    27. (2003). QT and RR intervals in conscious and anaesthetized guinea pigs with highly varying RR intervals and given QTc-lengthening test articles.
    28. (1999). QT interval prologation by noncardiovascular drugs: issues and solutions for novel drug development.
    29. (2005). QT PRODACT: in vivo QT assay in anesthetized dog for detecting the potential for QT interval prolongation by human pharmaceuticals.
    30. (2004). QT prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary screening of torsadogenicity of drugs and drug candidates.
    31. (2003). QTc prolongation due to propranolol overdose.
    32. (2003). Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development.
    33. (2008). Safety Pharmacology Society: 7th annual meeting
    34. (2001). Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes.
    35. (1999). Sustained QT prolongation induced by tacrolimus in guinea pigs.
    36. (2003). The impact of drug-induced QT interval prolongation on drug discovery and development.
    37. (1994). The novel class III antiarrhythmics NE-10064 and NE10133 inhibit IsK channels expressed in Xenopus oocytes and IKs in guinea pig cardiac myocytes.
    38. (1986). The pharmacokinetics of droperidol in anesthetized patients.
    39. (2000). The pharmacokinetics of ziprasidone in subjects with normal and impaired renal function.
    40. (1990). Torsades de pointes occurring in association with terfenadine use.
    41. (2002). Towards a drug concentration effect relationship for QT prolongation and torsade de pointes.
    42. (2001). Tpeak Tend interval as an index of transmural dispersion of repolarization.
    43. (2004). Variability in the measurement of hERG potassium channel inhibition: effects of temperature and stimulus pattern.

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