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Int J Clin Exp Med. 2015 Dec 15;8(12):22310-8. eCollection 2015.

Evaluation of the impact of Flos Daturae on rat hepatic cytochrome P450 enzymes by cocktail probe drugs.

International journal of clinical and experimental medicine

Peiwu Geng, Shuanghu Wang, Chunjie Wang, Jianmiao Chen, Lijing Zhang, Suping Yang, Congcong Wen, Yunfang Zhou, Meiling Zhang

Affiliations

  1. The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui Lishui 323000, China.
  2. Special Procurement Ward, First Affiliated Hospital of Soochow University Suzhou 215006, China.
  3. Analytical and Testing Center of Wenzhou Medical University Wenzhou 325035, China.

PMID: 26885208 PMCID: PMC4729994

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.

Keywords: CYP450; Flos Daturae; UPLC-MS/MS; cocktail; rat

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