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Titolo:
The preclinical assessment of the risk for QT interval prolongation
Autore:
Champeroux, P; Martel, E; Vannier, C; Blanc, V; Leguennec, JY; Fowler, J; Richard, S;
Indirizzi:
CERB, Chemin Montifault, F-18800 Baugy, France CERB Baugy France F-18800CERB, Chemin Montifault, F-18800 Baugy, France Fac Sci, CNRS UMR 6542, Lab Physiol Cellules Cardiaques & Vasc, F-37200 Tours, France Fac Sci Tours France F-37200 es Cardiaques & Vasc, F-37200 Tours, France The Ship, Beccles NR34 9BA, Suffolk, England The Ship Beccles Suffolk England NR34 9BA cles NR34 9BA, Suffolk, England
Titolo Testata:
THERAPIE
fascicolo: 1, volume: 55, anno: 2000,
pagine: 101 - 109
SICI:
0040-5957(200001/02)55:1<101:TPAOTR>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
TORSADE-DE-POINTES; RABBIT PURKINJE-FIBERS; IN-VITRO; HEART-RATE; TERFENADINE; ASTEMIZOLE; VIVO; MODEL; DOGS;
Keywords:
QT interval prolongation; proarrhythmic risk; preclinical assessment; electrocardiogram; Purkinje fibres;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Champeroux, P CERB, Chemin Montifault, F-18800 Baugy, France CERB Baugy France F-18800 ontifault, F-18800 Baugy, France
Citazione:
P. Champeroux et al., "The preclinical assessment of the risk for QT interval prolongation", THERAPIE, 55(1), 2000, pp. 101-109

Abstract

Some drugs have been reported to induce severe ventricular arrhythmias, including torsades de pointes, and have been responsible in some cases for sudden death of patients. Although the mechanisms of these arrhythmias are not well understood, they are often, but not always, associated with QT interval prolongation. Regulatory authorities (CPMP in Europe) have recently pointed out the necessity to assess most carefully the potential, especially of noncardiovascular drugs, for QT interval prolongation. Different methodological approaches are presented in this paper and experimental protocols are suggested; limitations and advantages of the presently available in vitroand in vivo models are discussed. It appears that both in villa and in vivo approaches are complementary. In particular it is pointed out that only the in vitro models using isolated cardiac tissues (Purkinje fibres or papillary muscles) enable assessment of the drug properties under low cardiac rhythm conditions. This model allows us to mimic pathological situations of long QT interval (such as acquired or congenital long QT syndrome) in which most of the major clinical problems are encountered. Finally, a strategy for the preclinical assessment of the potential of a molecule for QT intervalprolongation is presented.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 19:48:12