title: The effect of MS-275 on CYP450 isoforms activity in rats by cocktail method.
abstract: MS-275, is a potent, class I selective histone deacetylase inhibitor currently in clinical trials for the cure of several types of cancer. The influence of MS-275 on the activities of CYP450 isoforms CYP2B6, CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP2C19 were evaluated by cocktail method. The rats were randomly divided into MS-275 group (Low, Medium, High) and control group. The MS-275 group rats were given 12.3, 24.5, 49 mg/kg (Low, Medium, High) MS-275 by continuous intragastric administration for 7 days. The six probe drugs were given to rats through intragastric administration, and the plasma concentration were determinated by UPLC-MS/MS. The result of MS-275 group compared to control group, there were statistical pharmacokinetics difference for bupropion, phenacetin, tolbutamide, metroprolol, midazolam and omeprazole. Continuous intragastric administration for 7 days may induce the activities of CYP2B6, CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP2C19 of rats, and may induce the hepatocytes apoptosis. This may give advising for reasonable drug use after co-uesd with MS-275.
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Pharmaceutical Industry Shanghai 200437, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory Animal Centre of Wenzhou Medical University 325035, Wenzhou, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Hu
authors.affiliation: Laboratory Animal Centre of Wenzhou Medical University 325035, Wenzhou, China.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Guanyang
authors.initials: G
authors.lastname: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001549:Benzamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020033:Protein Isoforms / Q000378:metabolism*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D020033:Protein Isoforms; D011725:Pyridines; C118739:entinostat; D003577:Cytochrome P-450 Enzyme System
keywords: CYP450; HDAC; MS-275; UPLC-MS/MS; cocktail; rat