Tolerability and toxicological profile of pixantrone (Pixuvri (R)) in juvenile mice. Comparative study with doxorubicin

作者：Longo Monica^*; Della Torre Paola; Allievi Cecilia; Morisetti Alberto; Al Fayoumi Suliman; Singer Jack W

来源：Reproductive Toxicology, 2014, 46: 20-30.

DOI：10.1016/j.reprotox.2014.02.006

• Pixuvri
• Pixantrone
• Doxorubicin
• Juvenile
• Preclinical
• Anticancer

The tolerability of pixantrone dimaleate (Pixuvri (R)), an aza-anthracenedione for non-Hodgkin lymphoma, was assessed in juvenile mice after intraperitoneal injection.
Twenty animals/sex/dose received pixantrone 15 or 27 mg/kg/day on Post-Natal-Days (PND) 10, 13, 17, 20, 35, 39 and 42 in comparison with doxorubicin, 3 mg/kg/day. Animals were sacrificed on PND 42, 73 and 96.
All pixantrone animals survived, while doxorubicin induced 52.5% mortality and the surviving animals were sacrificed early due to severe toxicity. Recoverable bone marrow toxicity (pixantrone), and toxicity to thymus and reproductive organs (pixantrone, doxorubicin) were observed without nephro- or hepatotoxicity. Pixantrone was measurable in plasma up to 2 h (occasionally 6 h) post-dose. At PND 42, mean C-max and AUC values increased proportionally with dose, without gender difference or accumulation.
Pixantrone showed minimal cardiotoxicity in males and negligible in females at PND 96. Doxorubicin induced significant heart weight reduction at PND 42, however early sacrifice impeded further cardiac assessments.

• 出版日期2014-7