Report and recommendations of the workshop of the European Centre for the Validation of Alternative Methods for Drug-Induced Cardiotoxicity.
Cardiotoxicity is among the leading reasons for drug attrition and is therefore a core subject in non-clinical and clinical safety testing of new drugs. European Centre for the Validation of Alternative Methods held in March 2008 a workshop on "Alternative Methods for Drug-Induced Cardiotoxicity" in order to promote acceptance of alternative methods reducing, refining or replacing the use of laboratory animals in this field. This review reports the outcome of the workshop. The participants identified the major clinical manifestations, which are sensitive to conventional drugs, to be arrhythmias, contractility toxicity, ischaemia toxicity, secondary cardiotoxicity and valve toxicity. They gave an overview of the current use of alternative tests in cardiac safety assessments. Moreover, they elaborated on new cardiotoxicological endpoints for which alternative tests can have an impact and provided recommendations on how to cover them.
Stummann
Tina C
TC
European Centre for the Validation of Alternative Methods (ECVAM), T.P. 580, IHCP, JRC, European Commission, 21027 Ispra, VA, Italy.
Beilmann
Mario
M
Duker
Göran
G
Dumotier
Berengere
B
Fredriksson
J Magnus
JM
Jones
Robin L
RL
Hasiwa
Marina
M
Kang
Y James
YJ
Mandenius
Carl-Fredrik
CF
Meyer
Thomas
T
Minotti
Giorgio
G
Valentin
Y Jean-Pierre
YJ
Zünkler
Bernd J
BJ
Bremer
Susanne
S
D000826:Animal Testing Alternatives / Q000379:methods* / Q000639:trends; D000818:Animals; D000830:Animals, Laboratory; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control; D054715:Cardiotoxins / Q000009:adverse effects / Q000633:toxicity; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000517:prevention & control; D004493:Education / Q000639:trends; D005060:Europe; D006287:Health Planning Guidelines; D006801:Humans
D054715:Cardiotoxins