| Literature DB >> 26770498 |
Peiwu Geng1, Jinzhang Cai2, Shuanghu Wang1, Suping Yang3, Zezheng Liu3, Yingying Lin3, Congcong Wen3, Xianqin Wang4, Yunfang Zhou1, Meiling Zhang4.
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.Entities:
Keywords: CYP450; UPLC-MS/MS; cocktail; diphenoxylate; rat
Year: 2015 PMID： 26770498 PMCID： PMC4694398
Source DB: PubMed Journal: Int J Clin Exp Med ISSN： 1940-5901