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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.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 8 th  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.Co-administration of COP and florfenicol significantly increased AUC (0-∞) , MRT (0-∞) , and C max  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.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. 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. 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 8 th  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. Co-administration of COP and florfenicol significantly increased AUC (0-∞) , MRT (0-∞) , and C max  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. 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.

xenobiotica

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