恩诺沙星及其代谢物环丙沙星在欧洲鳗鲡体内的代谢动力学

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in European eel(Anguilla anguilla) after a single oral gavage

采用高效液相色谱法,研究药饵口灌给药途径下,恩诺沙星及其代谢物环丙沙星在欧洲鳗鲡(Anguilla anguilla)体内的药代动力学。欧洲鳗鲡口灌给药恩诺沙星10 mg/kg后,其血浆、肌肉和肝脏中药物时量曲线关系符合一级吸收的二室开放动力学模型。恩诺沙星在欧洲鳗鲡不同组织中分布较广,血浆、肌肉和肝脏的Vd分别为6.362 L/kg、8.081 L/kg和15.870 L/kg;恩诺沙星在鳗鲡体内消除较慢,在血浆、肌肉和肝脏中的消除半衰期(tβ1/2)分别为161.10 h、333.21 h和611.26 h,总体清除率(CLs)分别为27.4 mL/(kg.h)、16.8 g/(kg.h)和18.0 g/(kg.h)。代谢物环丙沙星在鳗鲡血浆、肌肉和肝脏中药物水平的变化趋势与恩诺沙星基本相似,呈现出多峰现象,但3种组织中环丙沙星出现第一个药峰时间分别为给药后第24小时、24小时和12小时,3种组织中环丙沙星峰值水平肝脏中最高、肌肉中次之、血浆中最低,环丙沙星在肌肉和肝脏中的消除速率比较缓慢。鉴于恩诺沙星和其代谢物环丙沙星在欧洲鳗鲡体内消除较慢,建议养成阶段使用其他药物。

The pharrnacokinetics, tissue metabolism and elimination of enrofloxacin and its metabolite ciprofloxacin were investigated in European eel, Anguilla anguilla, after administration by oral garage at a dosage of 10 mg/kg. Plasma and tissue concentrations of enrofloxacin and its metabolite ciprofloxacin were simultaneously determined by HPLC. The concentrations versus time in plasma, muscle and liver from the eel were well described by a two-department open model with first-order absorption. The present results indicated that enrofloxacin in European eel after oral dosing demonstrated that enrofloxacin had the ability to widely distribute to diverse tissues. The apparent volume of distribution of enrofloxacin of plasma, muscle and liver was 6. 362 L/kg, 8. 081 L/kg and 15. 870 L/kg, respectively. Enrofloxacin eliminated slowly. The elimination half-life （ tβ1/2） was 161.10 h, 333.21 h and 611.26 h, respectively, and the total body clearance （CLs） was 27.4 mL/（kg · h）, 16.8 g/（kg· h） and 18.0 g/（kg · h）, respectively. The metabolite ciprofloxacin concentration-time profiles of the plasma, muscle and liver presented similar trend. The multi-peak phenomenon were observed in the plasma, muscle and liver, but the first peak time was 24 h, 24 h and 12 h, respectively. The peak residue of metabolite ciprofloxacin was in liver, muscle and plasma, ordinally. The eliminating rate of ciprofloxacin from muscle and liver was very low. Considering that the eliminating rats of enrofloxacin and metabolite ciprofloxacin were very slow, we suggested that other antibacterial drugs used to prevent and treat bacterial diseases in the process of the eel＇s growing-up. [Journal of Fishery Sciences of China,2007,14（4） ：622 - 629]