PMID: 26770498Jan 16, 2016Paper

Effect of diphenoxylate on CYP450 isoforms activity in rats

International Journal of Clinical and Experimental Medicine
Peiwu GengMeiling Zhang

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.

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