恩诺沙星及其代谢产物在中华绒螯蟹血淋巴中的比较药代动力学

摘要

Several comparative pharmacokinetic data such as absorption, distribution and metabolism had been studied on enrofloxacin (ENR) in Chinese mitten -handed crab, Eriocheir sinensis with different water temperature, dose and dosage regime (oral administration and intramuscular injection).Results indicated that the hemolymph concentration - time data of Enrofloxacin in Eriocheir sinensis were best described by a twocompartment open model under different conditions.The main pharmacokinetics parameters by intramuscular administration with 10 mg/kg b.w.at 16 ℃: AUC 96.818mg/(L · h) ,Cmax 6.54 μg/mL, t1/2α 0.851h,t1/2β 95.415 h; the main pharmacokinetics parameters by intramuscular administration with 10 mg/kg b.w.at 25 ℃: AUC 168.457 mg /(L · h), Cmax 7.12 μg/mL, t1/2α 0.58h, t1/2β 88.833 h; the main pharmaeokinetics parameters by intramuscular administration with 20 mg/kg b.w.at 25 ℃: AUC 155.612 mg/( L · h) ,Cmax 11.045 μg/mL, t1/2α 5.239 h,t1/2β 88.378 h; the main pharmacokinetics parameters by oral administration with 10 mg/kg b.w.at 25 ℃:AUC 86.525 mg/L· h,Cmax 3.469 μg/mL, t1/2α8.071 h,t1/2β 61.842h.Results showed that the main pharmacokinetic parameters under different conditions were significantly different.The active metabolite ciprofloxaein (CIP) was checked in hemolymph of Eriocheir sinensis in all experiments, but all compartment models were not suitable for concentration -time data , and the concentration was very low, which indicated the poor capability of Eriocheir sinensis metabolizing enrofloxacin into eiprofloxacin.%研究了不同水温(16℃、25℃)、不同给药剂量(10 mg/kg、20 mg/kg)和不同给药方式(肌注、口灌)等条件下,恩诺沙星及其代谢产物环丙沙星在中华绒螯蟹体内的药代动力学,比较了不同条件下药物在蟹血淋巴中的吸收、分布和代谢的差异.结果表明,恩诺沙星在蟹血淋巴中的药-时数据符合开放式二室模型.16℃时以10 mg/kg剂量肌注给药后,恩诺沙星在蟹血淋巴的主要药代动力学参数为:AUC 96.818 mg/(L·h),Cmax6.54μg/mL,t1/2α0.851 h,t1/2β 95.415 h;25℃时以10 mg/kg剂量肌注给药后,恩诺沙星的主要药代动力学参数为:AUC168.457 mg/(L·h),Cmax7.12 μg/mL,t1/2α0.58h,t1/2β 88.833 h;25℃时以20mg/kg剂量肌注给药后,恩诺沙星的主要药代动力学参数为:AUC 155.612 mg/(L·h),Cmax11.045μg/mL,t1/2α5.239h,t1/2β 88.378 h;25℃时以10 mg/kg剂量口灌给药后,恩诺沙星的主要药代动力学参数为:AUC 86.525 mg/(L·h),Cmax 3.469μg/mL,t1/2α8.071h,t1/2β 61.842 h.不同条件下,恩诺沙星在蟹血淋巴中的主要药代动力学参数差异较大.恩诺沙星的活性代谢产物环丙沙星在各种给药条件下的蟹血淋巴中均能检出,但含量均处于较低值,且药-时数据不能用房室模型拟合,表明恩诺沙星在蟹体内只有极少部分代谢为环丙沙星.