恩诺沙星在罗氏沼虾体内的药物代谢动力学

Pharmacokinetics of Enrofloxacin in Macrobrachium rosenbergii

应用反相高效液相色谱法(RP-HPLC)研究了恩诺沙星在罗氏沼虾(Macrobrachiumrosenbergii)体内的药物代谢动力学。实验结果表明,恩诺沙星在血淋巴、肝胰腺、肌肉中的平均回收率分别为86.54%±2.39%、85.43%±2.75%、95.01%±1.99%,其代谢产物环丙沙星在血淋巴、肝胰腺、肌肉中的平均回收率分别为94.34%±8.30%、75.17%±5.42%、80.42%±1.67%;恩诺沙星及其代谢产物环丙沙星在三种组织中的平均日内精密度分别为3.39%±0.53%和3.92%±1.24%,而日间精密度分别为5.11%±1.73%和5.28%±2.10%。恩诺沙星、环丙沙星的最低检测限分别为0.02μg/ml和0.01μg/ml。罗氏沼虾以10mg/kg虾体重剂量单次肌肉注射给药后,血液中药物浓度即刻达到峰值,并迅速向组织中分布。实验数据经MCPKP药动学软件分析,恩诺沙星在血淋巴中的主要药物代谢动力学参数为:t1/2α为0.581h、t1/2β为69.315h、Vd/F为7.230L/kg、CL/F为0.035L/h.kg、K12为0.01/h、K21为0.005/h、AUC为291.898μg/ml.h、Tmax为0.083h、Cmax为6.293μg/ml;恩诺沙星在肝胰腺、肌肉组织中主要药动学参数:t1/2α为1.941h、0.000h;t1/2β为70.732h、59.456h;AUC为308.07μg/ml.h、217.039μg/ml.h。三种组织中均能检测到恩诺沙星的活性代谢产物环丙沙星,但含量均处于较低水平,药物浓度-时间数据经MCPKP药动学软件处理后,不能用开放性一室模型或二室模型拟合。

The pharmacokinetics of enrofloxacin （ENR） and ciprofloxacin （CIP） in hemolymph, hepatopancreas and muscle of the Macrobrachiura rosenbergii were investigated using the reverse-phase high performance liquid chromatography （RP-HPLC）. The average recovery rates of ENR in three tissues were 86.54 % ± 2.39 %, 85.43 % ± 2.75% ,and 95.01% ± 1.99% ,respectively,and the average recovery rate of CIP in three tissues were 94.34% ± 8.30% ,75.17% ± 5.42% ,and 80.42% ± 1.67% respectively in the three tissues;The intra-day precision rates of ENR and CIP were 3.39% ± 0.53% and 3.92% ± 1.24%, respectively, and the inter-day precision rates were 5.11% ± 1.73% and 5.28% ± 2.10%, respectively, The lowest detected limit of enrofloxacin in tissues was 0.02 μg/ml, and that of ciprofloxacin was 0.01 μg/ml,The data were analyzed with the pharmacokinetic computer program MCPKP. The main pharmacokinetic parameters of ENR in hemolymph were t1/2α 0.581 h, t 1/2β 69.315 h, Vd / F 7.230 Ukg, C1/F 0.035 Uh,kg, K12 0.01/h, K12 0.005/h,AUC 291.898 μg/ml·h, Tmax 0.083 h,and Cmax 6.293 μg/ml; the main pharmacokinetic parameters of NER in hepatopancreas and muscle were t1/2α 1.941 h, t1/2β 70.732 h, AUC 308.07 μg/ml· h, t1/2α, 0.000 h, tj1/2β 59.456 h, and AUC 217.039 μg/ml· h. Ciprofloxacin,the main active metabolite of enrofloxacin, exists in relatively low levels in all the main tissues of the shrimp, but its kinetics in the hemolymph could not be described by a one-or two-compartment open model.