title: In vitro assessment of cytochrome P450 inhibition and induction potential of felotaxel (SHR110008).
abstract: The purpose of this study was to assess the potential inhibitory and inductive effects of felotaxel on cytochrome P450 isozymes in vitro. The inhibitory effects of felotaxel on various CYP isozymes were determined in human liver microsomes. In addition, the ability of felotaxel to induce CYP enzymes in cultured human hepatocytes was evaluated. Results showed that felotaxel did not inhibit CYP1A2-, CYP2C9-, CYP2C19-, CYP2E1-, CYP2D6-, CYP2B6-, CYP2C8-, and mediated activities in human liver microsomes up to a concentration of 100 μM, while the inhibition (<30% inhibition) of CYP3A4 activities was observed at 100 μM felotaxel. In vitro felotaxel did not induce CYP1A2, CYP2C19, or CYP3A4/5 activities in cultured human hepatocytes. In present study, felotaxel has been identified as a potent inhibitor of metabolic activity of CYP3A4. Therefore, clinically relevant pharmacokinetic drug-drug interactions are likely to occur between felotaxel and co-administered substrates of these CYP3A4 isozymes. These findings provided some useful information for safe and effective use of felotaxel in clinical practice.
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 17 Changlexi Street, Xi'an 710032, Shaanxi, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: YanYan
authors.initials: Y
authors.lastname: Jia
authors.forename: ChengTao
authors.initials: C
authors.lastname: Lu
authors.forename: WenXing
authors.initials: W
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: YanRong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: LiKun
authors.initials: L
authors.lastname: Ding
authors.forename: AiDong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D043823:Taxoids; C571875:felotaxel; D003577:Cytochrome P-450 Enzyme System