Preclinical evaluation of potential nilotinib cardiotoxicity

Leuk Res. 2011 May;35(5):631-7. doi: 10.1016/j.leukres.2010.11.001. Epub 2010 Dec 3.

Abstract

In vitro, concentrations ≥ 10 μM of nilotinib were needed to induce markers of cytotoxicity, apoptosis, and endoplasmic reticulum stress in both neonatal rat ventricular myocytes, a putative target tissue, and non-target heart fibroblasts, indicating a lack of cardiomyocyte-specific nilotinib toxicity in vitro. In rats, oral nilotinib treatment at 80 mg/kg for 4 weeks induced increased heart weight; however, this was not associated with relevant histopathological changes or effects on heart function. Thus, nilotinib at and above clinically relevant concentrations (4.27 μM) did not induce overt cardiovascular pathologies or heart failure in vitro or in vivo under study conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cardiotoxins* / adverse effects
  • Cardiotoxins* / pharmacology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Heart / drug effects*
  • Heart / physiology
  • Heart Ventricles / anatomy & histology
  • Heart Ventricles / drug effects
  • Heart Ventricles / ultrastructure
  • Male
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology
  • Pyrimidines / adverse effects*
  • Pyrimidines / pharmacology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Ventricular Function / drug effects

Substances

  • Cardiotoxins
  • Pyrimidines
  • nilotinib