Preclinical Safety, Novartis Institutes for Biomedical Research, CH-4009 Basel, Switzerland.
Leuk Res. 2011 May;35(5):631-7. doi: 10.1016/j.leukres.2010.11.001. Epub 2010 Dec 3.
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.
在体外，需要浓度≥10 μM 的尼罗替尼才能诱导新生大鼠心室肌细胞（潜在的靶组织）和非靶心成纤维细胞的细胞毒性、细胞凋亡和内质网应激标志物，表明尼罗替尼在体外缺乏心肌细胞特异性毒性。在大鼠中，口服尼罗替尼 80 mg/kg 治疗 4 周会导致心脏重量增加；然而，这与相关的组织病理学变化或对心脏功能的影响无关。因此，在研究条件下，尼罗替尼在临床相关浓度（4.27 μM）及以上时，不会在体外或体内引起明显的心血管病变或心力衰竭。
