甲苯咪唑在银鲫体内的药代动力学研究

Pharmacokinetics of mebendazole in Johnny carp( Carassius auratus gibelio)

采用高效液相色谱法检测甲苯咪唑(MBZ)及其代谢物氨基甲苯咪唑(MBZ-NH2)和羟基甲苯咪唑(MBZ-OH)在银鲫(Carassius auratus gibelio)血浆及组织中的浓度,数据经3P97药代动力学程序分析。结果表明:(25±1)℃的水温条件下,银鲫单剂量口灌MBZ20mg·kg-1,血药经时过程符合二室开放式模型。主要药代动力学参数为:吸收速率常数Ka0.235h-1;消除半衰T(1/2)β52.26h;药时曲线下面积AUC180.07μg·h·mL-1;表观容积分布Vd/F2.465L·kg-1;清除率CL(s)0.111mL·h-1·kg-1;达峰时间T(peak)6.20h;质量浓度Cmax4.14μg·mL-1。与哺乳类相比,MBZ在银鲫体内吸收较慢,消除半衰期明显延长,药代动力学参数也有较大差异。建议在做到合理用药的同时加强药物检测力度。

The concentrations of mebendazole（MBZ） and its metabolites aminomebendazole（MBZ-NH2）and hydroxymebendazole（MBZ-OH）were determined by using the High Performance Liquid Chromatography. The data were analyzed with the pharmacokinetic computer program 3P97. The results indicated that when Johnny carp（Carassius auratus gibelio） took single-dose MBZ 20 mg·kg^-1 at（ 25±1） ℃ by oral addministration,the plasma concentration- time course of MBZ could be described by a two-compartment open model. The main pharmacokinetic parameters were as follows：The absorption rate constant（ Ka） of MBZ was found to be 0.235 h^-1,whereas the elimination half-life（ T1/2β） of the drug was 52.26 h. The area under the serum concentraction-time cure（ AUC） was 180.07 μg·h·mL^-1,and the distribution volume（ Vd /F） of MBZ was computed as 2.465 L·kg^-1. The total clearance of MBZ（ CLs） was estimated to be 0.111 mL·h^-1·kg^-1whereas the time-point of maximum plasma concentraction of the drug（ Tpeak） and the maximum plasma concentraction（ Cmax） were calculated as 6.20 h and 4.14 μg·mL^-1. Compared with mammals, in silver carp the MBZ is absorbed slowly and the elimination half-time is obviously long; the pharmacokinetic parameters are also different. So the detection should be intensified for the food security.