[Pertinence of animal and human models in the evaluation of ventricular anti-arrhythmia agents].
The development of antiarrhythmic agents for the treatment of ventricular arrhythmias depends to a large extent on their effects in different animal and human models. The clinical relevance of the data so obtained is debatable. Firstly, in vitro animal models of arrhythmias are not very predictive of the multiple clinical forms of ventricular arrhythmias. Secondly, the intermediary criteria of evaluation of the effects of antiarrhythmic drugs in humans are generally not valid in terms of criteria of substitution for the evaluation of therapeutic effects. Nevertheless, cellular and hemodynamic studies of the electrophysiological properties of drugs are essential for correct clinical usage of antiarrhythmics. They help predict the principal clinical electrocardiographic changes and their modulation with respect to parameters such as ischemia or heart rate, their hemodynamic tolerance and certain undesirable, especially proarrhythmic, effects. However, the clinical pertinence of these studies remains limited for a number of reasons. In particular, most antiarrhythmic agents have multiple electrophysiological effects, the resultant of which is difficult to predict in the clinical situation. In addition, many of these drugs have active metabolites, the formation of which varies from person to person, which also reduces the clinical relevance of studies of the parent molecule alone. Clinical trials in appropriate patient populations should therefore be preferred to the multiplication of studies on experimental models of uncertain relevance.
Funck-Brentano
C
C
Unité de pharmacologie clinique, hôpital Saint-Antoine, Paris.
Le Heuzey
J Y
JY
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D005117:Cardiac Complexes, Premature / Q000188:drug therapy; D004195:Disease Models, Animal; D004285:Dogs; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D004594:Electrophysiology; D006801:Humans; D017180:Tachycardia, Ventricular / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents
Pertinence clinique des modèles animaux et humains pour l'évaluation des antiarythmiques ventriculaires.