Evaluation of drug-induced QT interval prolongation: implications for drug approval and labelling.

摘要: Assessment of proarrhythmic toxicity newly developed drugs attracts significant attention from drug developers and regulatory agencies. Although no guidelines exist for such assessment, the present experience allows several key suggestions to be made an appropriate technology proposed. Several different in vitro preclinical models that, many instances, correctly predict clinical outcome. However, correspondence between is not absolute. None available has been demonstrated more predictive and/or superior others. Generally, compounds that do generate any adverse signal are less likely lead cardiac humans. Nevertheless, differences likelihood offer guarantee compared with entities a signal. Thus, investigations probabilistic answers possibility both false positive negative findings. Clinical assessment drug-induced QT interval prolongation crucially dependent on quality electrocardiographic data appropriateness analyses. An integral part this precise heart rate correction interval, which shown require QT/RR relationship each study individual. The numbers electrocardiograms required larger than usually obtained pharmacokinetic studies. safety considerations need early phase I/II Once established studies, large III studies postmarketing surveillance can limited strict designs. incidence torsade de pointes tachycardia varies 1 5% clearly (e.g. quinidine) hundreds thousands still considered unsafe terfenadine, cisapride). recording during offers guarantee, premarketing evaluation rely changes. since only indirect surrogate predisposition induction tachycardia, conclusion safe should reserved until reviewed. area drug-related fast evolving. academic perspective includes identification markers focused simple measurement, as well individuals increased risk pointes. careful adaptation new research