کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2550278 1124545 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ILSI-HESI cardiovascular safety subcommittee initiative: Evaluation of three non-clinical models of QT prolongation
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
ILSI-HESI cardiovascular safety subcommittee initiative: Evaluation of three non-clinical models of QT prolongation
چکیده انگلیسی

IntroductionDrugs that delay cardiac repolarization pose potential safety risks to patients and cause serious regulatory concern because of the link between QT interval prolongation and the potentially fatal arrhythmia torsades de pointes (TdP). Predicting which drugs will cause TdP is an inexact and difficult science. The utility of non-clinical assays was not well understood due in part to variability in methods, species, and consistency in the assays reported in the literature. The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) outlined a set of studies to determine how well selected commonly used non-clinical assays identified compounds known to cause TdP and prolong QT interval in humans.MethodsCompounds known to prolong ventricular repolarization and compounds considered safe by years of clinical use were tested in three assays: HERG ionic current, Purkinje fiber repolarization, and in vivo QT studies in conscious telemeterized dogs.ResultsThe data from each of these assays demonstrate that compounds that may pose a proarrhythmia risk for patients can be distinguished from those that are considered safe.DiscussionTaken collectively, the in-vitro and in-vivo preclinical results can be integrated to develop an accurate preclinical risk assessment to support clinical safety.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmacological and Toxicological Methods - Volume 54, Issue 2, September–October 2006, Pages 116–129
نویسندگان
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