Shimon Nakashima, Rei Sato, Tatsuki Fukami, Takashi Kudo, Shiori Hashiba, Gaku Morinaga, Masataka Nakano, Eva Ludwig-Schwellinger, Akiko Matsui, Naoki Ishiguro, Thomas Ebner, Miki Nakajima
Nintedanib, which is used to treat idiopathic pulmonary fibrosis and non-small cell lung cancer, is metabolized to a pharmacologically inactive carboxylate derivative, BIBF1202, via hydrolysis and subsequently by glucuronidation to BIBF1202 acyl-glucuronide (BIBF1202-G). Since BIBF1202-G contains an ester bond, it can be hydrolytically cleaved to BIBF1202. In this study, we sought to characterize these metabolic reactions in the human liver and intestine. Nintedanib hydrolysis was detected in human liver microsomes (HLM) ( CL int : 102...
March 16, 2023: Drug Metabolism and Disposition: the Biological Fate of Chemicals