The roles of cytochrome P450 and P-glycoprotein in the pharmacokinetics of florfenicol in chickens

Document Type: Full paper (Original article)

Authors

1 Department of Basic Veterinary Medicine, Animal College of Science and Technology, Henan University of Science and Technology, Luoyang 471023, China

2 Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China

3 Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

Abstract

The effects of three selective oral inhibitors, fluvoxamine (FLU), ketoconazole (KET), and verapamil (VER), on the pharmacokinetics (PK) of florfenicol (FFC) were investigated in chickens. The chickens were administered orally with saline solution (SAL), FLU (60 mg/kg), KET (25 mg/kg), or VER (9 mg/kg) for 7 consecutive days. Florfenicol was given to the chickens at a single dose of 30 mg/kg orally. Blood samples were collected from each chicken at 0 to 12 h post-administration of FFC. The plasma concentration of FFC was analyzed by high-performance liquid chromatography (HPLC). The AUC of FFC increased and the CLs of FFC decreased with oral co-administration of KET in chickens, and the Cmax of FFC increased with VER. While the AUC, the CLs and the Cmax of FFC were all invariable with FLU. These data suggested that CYP 3A played a key role in the PK of FFC in chickens, however, P-glycoprotein (P-gp) and CYP 1A did not. The results imply that the adverse drug-drug interaction may occur in the use of FFC if the co-administrated drugs are the substrates, inducers or inhibitors of CYP 3A or/and P-gp.

Keywords


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