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Xenobiotica
the fate of foreign compounds in biological systems
Volume 53, 2023 - Issue 3
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Animal Pharmacokinetics and Metabolism

Coptisine modulates the pharmacokinetics of florfenicol by targeting CYP1A2, CYP2C11 and CYP3A1 in the liver and P-gp in the jejunum of rats: a pilot study

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Pages 207-214 | Received 23 Mar 2023, Accepted 03 May 2023, Published online: 15 May 2023
 

Abstract

  1. Coptisine (COP) is the main active ingredient of Coptis chinensis. In Chinese veterinary clinics, Coptis chinensis is commonly used alongside florfenicol to treat intestinal infections. The goal of this study was to investigate the impact of COP co-administration on the pharmacokinetics of florfenicol in rats.

  2. Male Sprague-Dawley rats were orally administered COP (50 mg/kg BW) or sterile water for 7 consecutive days, followed by a single oral dose of florfenicol (25 mg/kg BW) on the 8th day. Pharmacokinetics of florfenicol were analysed using non-compartmental methods, while expression levels of cytochrome P450 (CYP) isoforms in the liver and P-glycoprotein (P-gp) in the jejunum were measured using real-time RT-PCR, Western blot and immunohistochemical analyses.

  3. Co-administration of COP and florfenicol significantly increased AUC(0-∞), MRT(0-∞), and Cmax of florfenicol, while CLz/F was significantly decreased. COP down-regulated the expression of CYP1A2, CYP2C11, and CYP3A1 in the liver, as well as P-gp in the jejunum.

  4. These findings suggest that co-administration of COP with florfenicol alters the pharmacokinetics of florfenicol in rats. The down-regulation of CYP and P-gp expression may contribute to this effect. Therefore, the co-administration of COP with florfenicol may enhance the prophylactic or therapeutic efficacy of florfenicol in veterinary practice.

Disclosure statement

All the authors have declared that there are no conflicts of interest.

Additional information

Funding

This study was supported by the Program Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System (SCCXTD-2020-18), the Special Project for Basic Scientific Research and Operating Expenses of The Public Welfare Research Institute of Sichuan Province (SASA202104), Major Science and Technology Projects of the "14th Five Year Plan" in Sichuan Province (2021ZDZX0010-2) and Sichuan Provincial Scientific Research Institute Scientific and Technological Achievements Transformation Project (2022JDZH0028).

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