The Experts below are selected from a list of 3 Experts worldwide ranked by ideXlab platform
Jeanpierre Valentin - One of the best experts on this subject based on the ideXlab platform.
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a rabbit langendorff Heart Proarrhythmia model predictive value for clinical identification of torsades de pointes
British Journal of Pharmacology, 2006Co-Authors: C L Lawrence, Matthew Bridglandtaylor, C E Pollard, Tim Hammond, Jeanpierre ValentinAbstract:Background and purpose: The rabbit isolated Langendorff Heart model (SCREENIT) was used to investigate the proarrhythmic potential of a range of marketed drugs or drugs intended for market. These data were used to validate the SCREENIT model against clinical outcomes. Experimental approach: Fifty-five drugs, 3 replicates and 2 controls were tested in a blinded manner. Proarrhythmia variables included a 10% change in MAPD60, triangulation, instability and reverse frequency-dependence of the MAP. Early afterdepolarisations, ventricular tachycardia, TdP and ventricular fibrillation were noted. Data are reported at nominal concentrations relative to EFTPCmax. Proarrhythmic scores were assigned to each drug and each drug category. Key results: Category 1 and 2 drugs have the highest number of Proarrhythmia variables and overt Proarrhythmia while Category 5 drugs have the lowest, at every margin. At 30-fold the EFTPCmax, the mean proarrhythmic scores are: Category 1, 101724; Category 2, 101714; Category 3, 72720; Category 4, 59716 and Category 5, 2279 points. Only drugs in Category 5 have mean proarrhythmic scores, below 30-fold, that remain within the Safety Zone. Conclusions and Implications: A 30-fold margin between effects and EFTPCmax is sufficiently stringent to provide confidence to proceed with a new chemical entity, without incurring the risk of eliminating potentially beneficial drugs. The model is particularly useful where compounds have small margins between the hERG IC50 and predicted EFTPCmax. These data suggest this is a robust and reliable assay that can add value to an integrated QT/TdP risk assessment. British Journal of Pharmacology (2006) 149, 845–860. doi:10.1038/sj.bjp.0706894; published online 9 October 2006
C L Lawrence - One of the best experts on this subject based on the ideXlab platform.
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a rabbit langendorff Heart Proarrhythmia model predictive value for clinical identification of torsades de pointes
British Journal of Pharmacology, 2006Co-Authors: C L Lawrence, Matthew Bridglandtaylor, C E Pollard, Tim Hammond, Jeanpierre ValentinAbstract:Background and purpose: The rabbit isolated Langendorff Heart model (SCREENIT) was used to investigate the proarrhythmic potential of a range of marketed drugs or drugs intended for market. These data were used to validate the SCREENIT model against clinical outcomes. Experimental approach: Fifty-five drugs, 3 replicates and 2 controls were tested in a blinded manner. Proarrhythmia variables included a 10% change in MAPD60, triangulation, instability and reverse frequency-dependence of the MAP. Early afterdepolarisations, ventricular tachycardia, TdP and ventricular fibrillation were noted. Data are reported at nominal concentrations relative to EFTPCmax. Proarrhythmic scores were assigned to each drug and each drug category. Key results: Category 1 and 2 drugs have the highest number of Proarrhythmia variables and overt Proarrhythmia while Category 5 drugs have the lowest, at every margin. At 30-fold the EFTPCmax, the mean proarrhythmic scores are: Category 1, 101724; Category 2, 101714; Category 3, 72720; Category 4, 59716 and Category 5, 2279 points. Only drugs in Category 5 have mean proarrhythmic scores, below 30-fold, that remain within the Safety Zone. Conclusions and Implications: A 30-fold margin between effects and EFTPCmax is sufficiently stringent to provide confidence to proceed with a new chemical entity, without incurring the risk of eliminating potentially beneficial drugs. The model is particularly useful where compounds have small margins between the hERG IC50 and predicted EFTPCmax. These data suggest this is a robust and reliable assay that can add value to an integrated QT/TdP risk assessment. British Journal of Pharmacology (2006) 149, 845–860. doi:10.1038/sj.bjp.0706894; published online 9 October 2006
Matthew Bridglandtaylor - One of the best experts on this subject based on the ideXlab platform.
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a rabbit langendorff Heart Proarrhythmia model predictive value for clinical identification of torsades de pointes
British Journal of Pharmacology, 2006Co-Authors: C L Lawrence, Matthew Bridglandtaylor, C E Pollard, Tim Hammond, Jeanpierre ValentinAbstract:Background and purpose: The rabbit isolated Langendorff Heart model (SCREENIT) was used to investigate the proarrhythmic potential of a range of marketed drugs or drugs intended for market. These data were used to validate the SCREENIT model against clinical outcomes. Experimental approach: Fifty-five drugs, 3 replicates and 2 controls were tested in a blinded manner. Proarrhythmia variables included a 10% change in MAPD60, triangulation, instability and reverse frequency-dependence of the MAP. Early afterdepolarisations, ventricular tachycardia, TdP and ventricular fibrillation were noted. Data are reported at nominal concentrations relative to EFTPCmax. Proarrhythmic scores were assigned to each drug and each drug category. Key results: Category 1 and 2 drugs have the highest number of Proarrhythmia variables and overt Proarrhythmia while Category 5 drugs have the lowest, at every margin. At 30-fold the EFTPCmax, the mean proarrhythmic scores are: Category 1, 101724; Category 2, 101714; Category 3, 72720; Category 4, 59716 and Category 5, 2279 points. Only drugs in Category 5 have mean proarrhythmic scores, below 30-fold, that remain within the Safety Zone. Conclusions and Implications: A 30-fold margin between effects and EFTPCmax is sufficiently stringent to provide confidence to proceed with a new chemical entity, without incurring the risk of eliminating potentially beneficial drugs. The model is particularly useful where compounds have small margins between the hERG IC50 and predicted EFTPCmax. These data suggest this is a robust and reliable assay that can add value to an integrated QT/TdP risk assessment. British Journal of Pharmacology (2006) 149, 845–860. doi:10.1038/sj.bjp.0706894; published online 9 October 2006
C E Pollard - One of the best experts on this subject based on the ideXlab platform.
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a rabbit langendorff Heart Proarrhythmia model predictive value for clinical identification of torsades de pointes
British Journal of Pharmacology, 2006Co-Authors: C L Lawrence, Matthew Bridglandtaylor, C E Pollard, Tim Hammond, Jeanpierre ValentinAbstract:Background and purpose: The rabbit isolated Langendorff Heart model (SCREENIT) was used to investigate the proarrhythmic potential of a range of marketed drugs or drugs intended for market. These data were used to validate the SCREENIT model against clinical outcomes. Experimental approach: Fifty-five drugs, 3 replicates and 2 controls were tested in a blinded manner. Proarrhythmia variables included a 10% change in MAPD60, triangulation, instability and reverse frequency-dependence of the MAP. Early afterdepolarisations, ventricular tachycardia, TdP and ventricular fibrillation were noted. Data are reported at nominal concentrations relative to EFTPCmax. Proarrhythmic scores were assigned to each drug and each drug category. Key results: Category 1 and 2 drugs have the highest number of Proarrhythmia variables and overt Proarrhythmia while Category 5 drugs have the lowest, at every margin. At 30-fold the EFTPCmax, the mean proarrhythmic scores are: Category 1, 101724; Category 2, 101714; Category 3, 72720; Category 4, 59716 and Category 5, 2279 points. Only drugs in Category 5 have mean proarrhythmic scores, below 30-fold, that remain within the Safety Zone. Conclusions and Implications: A 30-fold margin between effects and EFTPCmax is sufficiently stringent to provide confidence to proceed with a new chemical entity, without incurring the risk of eliminating potentially beneficial drugs. The model is particularly useful where compounds have small margins between the hERG IC50 and predicted EFTPCmax. These data suggest this is a robust and reliable assay that can add value to an integrated QT/TdP risk assessment. British Journal of Pharmacology (2006) 149, 845–860. doi:10.1038/sj.bjp.0706894; published online 9 October 2006
Tim Hammond - One of the best experts on this subject based on the ideXlab platform.
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a rabbit langendorff Heart Proarrhythmia model predictive value for clinical identification of torsades de pointes
British Journal of Pharmacology, 2006Co-Authors: C L Lawrence, Matthew Bridglandtaylor, C E Pollard, Tim Hammond, Jeanpierre ValentinAbstract:Background and purpose: The rabbit isolated Langendorff Heart model (SCREENIT) was used to investigate the proarrhythmic potential of a range of marketed drugs or drugs intended for market. These data were used to validate the SCREENIT model against clinical outcomes. Experimental approach: Fifty-five drugs, 3 replicates and 2 controls were tested in a blinded manner. Proarrhythmia variables included a 10% change in MAPD60, triangulation, instability and reverse frequency-dependence of the MAP. Early afterdepolarisations, ventricular tachycardia, TdP and ventricular fibrillation were noted. Data are reported at nominal concentrations relative to EFTPCmax. Proarrhythmic scores were assigned to each drug and each drug category. Key results: Category 1 and 2 drugs have the highest number of Proarrhythmia variables and overt Proarrhythmia while Category 5 drugs have the lowest, at every margin. At 30-fold the EFTPCmax, the mean proarrhythmic scores are: Category 1, 101724; Category 2, 101714; Category 3, 72720; Category 4, 59716 and Category 5, 2279 points. Only drugs in Category 5 have mean proarrhythmic scores, below 30-fold, that remain within the Safety Zone. Conclusions and Implications: A 30-fold margin between effects and EFTPCmax is sufficiently stringent to provide confidence to proceed with a new chemical entity, without incurring the risk of eliminating potentially beneficial drugs. The model is particularly useful where compounds have small margins between the hERG IC50 and predicted EFTPCmax. These data suggest this is a robust and reliable assay that can add value to an integrated QT/TdP risk assessment. British Journal of Pharmacology (2006) 149, 845–860. doi:10.1038/sj.bjp.0706894; published online 9 October 2006
