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Xenobiotica
the fate of foreign compounds in biological systems
Volume 53, 2023 - Issue 5
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Animal Pharmacokinetics and metabolism

Impact of tectoridin on the pharmacokinetics of florfenicol via targeting cytochrome P450 and P-glycoprotein of rats

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Pages 429-437 | Received 03 Aug 2023, Accepted 16 Sep 2023, Published online: 02 Oct 2023
 

Abstract

  1. Belamcanda chinensis (L.) DC, commonly used with florfenicol in Chinese veterinary clinics for respiratory tract infections, contains the major effective isoflavone, tectoridin (TEC). This study aimed to investigate the impact of TEC co-administration on the pharmacokinetics of florfenicol in vivo.

  2. Male rats received oral TEC (50 mg/kg BW) or sterile water for seven days, followed by a single oral dose of florfenicol (25 mg/kg BW) on the 8th day. Non-compartmental methods analysed the pharmacokinetics of florfenicol, while real-time reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analyses measured expression levels of cytochrome P450 (CYP) isoforms in the liver and P-glycoprotein (P-gp) in the jejunum.

  3. TEC significantly decreased florfenicol’s AUC(0–∞), MRT(0–∞), t1/2z, Vz/F, and Cmax by 24.75%, 18.43%, 55.47%, 43.05%, and 19.48%, while increasing CLz/F by 33.33%. TEC also up-regulated hepatic CYP1A2 and CYP3A1 mRNA expression, as well as intestinal MDR1, by 1.39-fold, 1.85-fold, and 1.65-fold. This coincided with a respective increase in protein expression by 1.37-fold, 1.39-fold, and 1.43-fold.

  4. These findings suggest that TEC-induced alterations in the pharmacokinetics of florfenicol may be attributed to increased CYP and P-gp expression. Further investigations are warranted to understand the implications of these findings on the clinical effectiveness of florfenicol in veterinary practice.

Acknowledgements

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).

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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