Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies.
Cytotoxic concentrations of imatinib mesylate (10-50 microM) were required to trigger markers of apoptosis and endoplasmic reticulum stress response in neonatal rat ventricular myocytes and fibroblasts, with no significant differences observed between c-Abl silenced and nonsilenced cells. In mice, oral or intraperitoneal imatinib treatment did not induce cardiovascular pathology or heart failure. In rats, high doses of oral imatinib did result in some cardiac hypertrophy. Multi-organ toxicities may have increased the cardiac workload and contributed to the cardiac hypertrophy observed in rats only. These data suggest that imatinib is not cardiotoxic at clinically relevant concentrations (5 microM).
Wolf
Armin
A
Preclinical Safety, Novartis Institutes for Biomedical Research, CH-4009 Basel, Switzerland.
Couttet
Philippe
P
Dong
Min
M
Grenet
Olivier
O
Heron
Marcia
M
Junker
Ursula
U
Laengle
Ulrich
U
Ledieu
David
D
Marrer
Estelle
E
Nussher
Anja
A
Persohn
Elke
E
Pognan
Francois
F
Rivière
Gilles-Jacques
GJ
Roth
Daniel Robert
DR
Trendelenburg
Christian
C
Tsao
Jeffrey
J
Roman
Danielle
D
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001483:Base Sequence; D001549:Benzamides; D017931:DNA Primers; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D000068877:Imatinib Mesylate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate