Toxicological and metabolic considerations for histone deacetylase inhibitors

INTRODUCTION: Vorinostat and romidepsin were the first histone deacetylase (HDAC) inhibitors (HDi) that fulfilled the preclinical promise of anticancer potential in clinical trials. Nevertheless, they merely opened a new chapter in the history of cancer therapy. Demonstration of their antitumor activity was a straightforward task in in vitro setting. Proving their efficacy in vivo was much more difficult, since the effects of an administrated drug strongly depend on its absorption, distribution, metabolism and excretion. AREAS COVERED: This article summarizes clinical data on the pharmacokinetic properties of HDi that are currently at more advanced stages of clinical development. Specific attention is paid to the metabolic pathways. Moreover, a comprehensive overview of HDi-related adverse effects is given. EXPERT OPINION: At this moment,…