title: Effect of acute paraquat poisoning on CYP450 isoforms activity in rats by cocktail method.
abstract: Paraquat is a highly effective contact herbicide that is marketed worldwide as a fantastical, non-selective compound for broadleaf weed control. As compared to most pesticides, paraquat is extremely toxic to humans and the lack of strategies to manage paraquat poisoning has resulted in high fatality rates. The rats were randomly divided into acute paraquat poisoning group and control group. The paraquat group rats were given 36 mg/kg paraquat by intragastric administration. The influence of acute paraquat poisoning on the activities of CYP450 isoforms CYP2B6, CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP2C19 were evaluated by cocktail method, they were responded by the changes of pharmacokinetic parameters of bupropion, phenacetin, tolbutamide, metoprolol, midazolam and omeprazole. The six probe drugs were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. In the results of paraquat group compared to control group, there was statistical pharmacokinetic difference for bupropion, tolbutamide, metoprolol, midazolam and omeprazole. Acute paraquat poisoning may induce the activities of CYP2C19, and inhibit of CYP2B6, CYP2C9, CYP2D6 and CYP3A4 in rats. This may give advising for reasonable drug use after acute paraquat poisoning.
authors.affiliation: Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Mengchun
authors.initials: M
authors.lastname: Chen
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Zezheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Function Experiment Teaching Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Ma
keywords: CYP450; UPLC-MS/MS; cocktail; paraquat; rat