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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
TLDR
The dataset confirms the widely-held belief that most drugs associated with TdP in humans are also associated with hERG K(+) channel block at concentrations close to or superimposed upon the free plasma concentrations found in clinical use.
Validation of a larval zebrafish locomotor assay for assessing the seizure liability of early-stage development drugs.
TLDR
This assay offers potential as a medium throughput screen aimed at the early drug discovery detection of this complex safety pharmacological endpoint, particularly considering the potential for throughput and likely positioning within a safety pharmacology front-loading screening cascade.
Ototoxin-induced cellular damage in neuromasts disrupts lateral line function in larval zebrafish
TLDR
Functional assessment revealed robust and significant attenuation of the innate startle, rheotactic and avoidance responses of 5 day old zebrafish larvae after treatment with a number of compounds previously shown to induce hair cell damage and loss.
Approaches to seizure risk assessment in preclinical drug discovery.
TLDR
The current techniques available to assess seizure risk are reviewed and how they may be combined in a rational step-wise cascade allowing more effective assessment of seizure risk is described.
Validation of the use of zebrafish larvae in visual safety assessment.
TLDR
The results suggest that the OMR assay in zebrafish could be useful in predicting the adverse effects of drugs on visual function in man and would support its potential as a screen for 'frontloading' safety pharmacology assessment of this endpoint in vivo.
Evaluation of a convenient method of assessing rodent visual function in safety pharmacology studies: effects of sodium iodate on visual acuity and retinal morphology in albino and pigmented rats and
TLDR
The method proved to be very convenient, and the stability of visual acuity in vehicle control rats over a 6-week period also demonstrated its suitability for inclusion in long-term toxicity studies.
Methods of collecting and evaluating non-clinical cardiac electrophysiology data in the pharmaceutical industry: results of an international survey.
TLDR
Current practice in the pharmaceutical industry for assessing the potential for QT interval prolongation by non-cardiovascular medicinal products is assessed, providing a snapshot of the practice prior to any internationally-agreed consensus on the most effective and efficient approaches to minimising the risk.
A framework to assess the translation of safety pharmacology data to humans.
TLDR
This strategy should contribute to the reduction of candidate drug attrition and a more appropriate use of animals and more accurate comparisons of models e.g. pharmacokinetic/phamacodynamic relationships as well as non-clinical and clinical outcomes for determining concordance.
The role of catecholamines in the production of ischaemia‐induced ventricular arrhythmias in the rat in vivo and in vitro
TLDR
The overall conclusion was that catecholamines were not necessary mediators of the early phase of ventricular arrhythmias in the rat, and those drugs which had demonstrable local anaesthetic properties also exerted significant antiarrhythmic effects.
Zebrafish assays as early safety pharmacology screens: paradigm shift or red herring?
TLDR
The purpose of this commentary is to take stock of the available zebrafish assays in the context of alternative mammalian cell-based assays, and of the validation outcomes to date.
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