Reproductive and developmental toxicity assessment of palbociclib, a CDK4/6 inhibitor, in Sprague-Dawley rats and New Zealand White rabbits

Reprod Toxicol. 2019 Sep:88:76-84. doi: 10.1016/j.reprotox.2019.07.016. Epub 2019 Jul 27.

Abstract

Palbociclib is a selective inhibitor of the cyclin-dependent kinase (CDK) 4/6, approved for the treatment of breast cancer. We assessed the potential effects of oral administration of palbociclib on reproduction and development. There were no effects on female or male fertility indices; however, in the male there was seminiferous tubule degeneration in the testes and secondary findings in the epididymides, lower testicular and epididymal weights, sperm density and motility. Palbociclib was not teratogenic in rats or rabbits; however, in the presence of maternal toxicity (lower maternal body weight gain and food consumption), low fetal body weights were observed in rats and small forepaw phalanges were noted in rabbits. There were, however, no adverse effects on the F1 generation in a pre- and post-natal developmental toxicity study in the rat.

Keywords: CDK4/6; Embryo-fetal development; Fertility; Palbociclib; Rabbit; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Embryonic Development / drug effects
  • Female
  • Fertility / drug effects
  • Fetal Development / drug effects
  • Male
  • Piperazines / toxicity*
  • Pyridines / toxicity*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Piperazines
  • Pyridines
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib