Effects of berberine on the pharmacokinetics of florfenicol and levels of cytochrome P450 3A37, multidrug resistance 1, and chicken xenobiotic-sensing orphan nuclear receptor mRNA expression in broilers

Abstract

Background: Berberine (BBR) is always used in combination with florfenicol for treating avian in China.

Objective: This study aims to investigate the effects of BBR on the pharmacokinetics of florfenicol in broilers.

Methods: Male broilers were randomly divided into the control group and the BBR group (BG). Note that 50 mg/kg BBR or sterile water was orally administrated to broilers. On the 8th day, florfenicol [30 mg/kg body weight (BW)] was orally administered to broilers in both groups. The plasma concentrations of florfenicol were determined by ultra-high-performance liquid chromatography (UHPLC). The levels of cytochrome P450 (CYP) 3A37, multidrug resistance 1 (MDR1), and chicken xenobiotic-sensing orphan nuclear receptor (CXR) mRNA expression in the liver and jejunum were determined by the real-time PCR.

Results: The results showed that the C_max , t_1/2z , MRT_(0-∞) , and AUC_(0-∞) of florfenicol in BG were significantly increased (by 55.71%, 28.32%, 35.19%, and 55.62%, respectively), while the T_max and CLz/F of florfenicol were significantly decreased (by 52.13% and 35.82%, respectively). In BG, the levels of CYP3A37, MDR1, and CXR mRNA expression in the liver were significantly decreased to 0.72-fold, 0.67-fold, and 0.59-fold, respectively, and the corresponding mRNA expression in the jejunum were significantly decreased to 0.66-fold, 0.55-fold, and 0.64-fold levels, respectively, relative to their levels in the control group.

Conclusions: BBR altered the pharmacokinetics of florfenicol, probably related to its inhibition of CYP3A37, MDR1, and CXR mRNA expression in the jejunum and liver.

Keywords: berberine; cytochrome P450; florfenicol; multidrug resistance 1; pharmacokinetics.