title: Effect of diphenoxylate on CYP450 isoforms activity in rats.
abstract: In order to investigate the effects of diphenoxylate on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B6, CYP2D6, CYP2C19, CYP1A2, CYP3A4, CYP2C9. The rats were randomly divided into diphenoxylate group (Low, Medium, High) and control group. The diphenoxylate group rats were given 12, 24, 48 mg/kg (Low, Medium, High) diphenoxylate by continuous intragastric administration for 7 days. Six probe drugs bupropion, metroprolol omeprazole, phenacetin, testosterone and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Statistical pharmacokinetics difference for omeprazole, phenacetin and tolbutamide in rats were observed by comparing diphenoxylate group with control group. Continuous 7 days-intragastric administration of diphenoxylate induces the activities of CYP2C19, CYP1A2 and CYP2C9 of rats. Induction of drug metabolizing enzyme by diphenoxylate would reduce the efficacy of other drug. Additionally, high dosage diphenoxylate may cause hepatotoxicity.
authors.affiliation: Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Wenzhou Medical University Lishui 323000, China.
authors.forename: Peiwu
authors.initials: P
authors.lastname: Geng
authors.affiliation: The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325000, China.
authors.forename: Jinzhang
authors.initials: J
authors.lastname: Cai
authors.affiliation: Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Wenzhou Medical University Lishui 323000, China.
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Yang
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: Yingying
authors.initials: Y
authors.lastname: Lin
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 UniversityWenzhou 325035, China; Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of JusticeShanghai 200063, China.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Wenzhou Medical University Lishui 323000, China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Analytical and Testing Center of Wenzhou Medical UniversityWenzhou 325035, China; Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Science, Ministry of JusticeShanghai 200063, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhang
keywords: CYP450; UPLC-MS/MS; cocktail; diphenoxylate; rat