title: Evaluation of the impact of Flos Daturae on rat hepatic cytochrome P450 enzymes by cocktail probe drugs.
abstract: Flos Daturae, known as "baimantuoluo" or "yangjinhua" in China, has been used for centuries in Traditional Chinese Medicine for the treatment of asthma, convulsions, pain, and rheumatism. To investigate the influences of Flos Daturae on the activities of rat CYP450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2B6, CYP2D6 and CYP3A4) using cocktail probe drugs in vivo. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (10 mg/kg), tolbutamide (1 mg/kg), omeprazole (10 mg/kg), bupropion (10 mg/kg), metoprolol (10 mg/kg) and testosterone (10 mg/kg), was intragastric administered to rats treated with a single low or high dose of Flos Daturae decotion for 7days. Blood samples collected at a series of time-points in plasma were determined by UPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 3.0. The results from the present in vivo study showed that Flos Daturae induce the activity of CYP2D6 enzyme with the decreased Cmax, AUC(0-∞) (P < 0.05) and the increased CL (P < 0.05). However, there were no significant differences of other probe drugs in plasma concentration and pharmacokinetic parameters. There were no significant effects on rat CYP1A2, CYP3A4, CYP2B6, CYP2C9 and CYP2C19 by Flos Daturae. Therefore, the resulting data suggested that caution was needed when Flos Daturae was co-administered with CYP2D6 substrates, which may result in treatment failure and herb-drug interactions.
authors.affiliation: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
authors.forename: Peiwu
authors.initials: P
authors.lastname: Geng
authors.affiliation: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Special Procurement Ward, First Affiliated Hospital of Soochow University Suzhou 215006, China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Wang
authors.affiliation: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
authors.forename: Jianmiao
authors.initials: J
authors.lastname: Chen
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: Suping
authors.initials: S
authors.lastname: Yang
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhang
keywords: CYP450; Flos Daturae; UPLC-MS/MS; cocktail; rat