吡喹酮及其主要代谢产物在草鱼体内代谢动力学研究

Pharmacokinetics Study on Praziquantel and Its Major Metabolites in Grass Crap

[目的]研究吡喹酮及其主要代谢产物在草鱼体内的代谢动力学规律。[方法]运用高效液相色谱法(HPLC),研究淡水草鱼在单次口灌给药10 mg/kg剂量条件下,鱼体各组织中吡喹酮(PZQ)及吡喹酮一羟基代谢物(M1)的药动学差异。[结果]草鱼血浆、肠道、肝脏和肾脏内PZQ在各个时间点的药物浓度存在极显著差异(P<0.01);PZQ在血浆、肠道、肝脏和肾脏的达峰时间分别为1.0、0.5、1.0和1.0 h,而药物峰浓度为0.41、0.45、0.72和0.44 mg/L,M1在血浆、肠道、肝脏和肾脏的达峰时间分别为48.0、0.5、6.0和48.0 h,而药物峰浓度为0.72、0.45、0.42和0.42 mg/g。这表明PZQ在草鱼体内吸收分布快,M1的达峰时间滞后于PZQ。二者达峰浓度相似表明M1是PZQ在草鱼体内主要代谢物。PZQ在血浆、肠道、肝脏和肾脏的消除半衰期(t_(1/2))分别为16.41、4.77、37.16和8.74 h,M1在血浆、肠道、肝脏和肾脏的消除半衰期(t_(1/2))分别为124、71、246和162 h,其消除半衰期明显比PZQ长,说明在鱼体中M1的残留时间比PZQ更长。[结论]在实际生产中,应注意对M1的检测。

[ Objective ] To study the pharmacokinetics laws of parziguantel （PZQ） and its major metabolites in grass erap. [ Method] Using high performance liquid chromatography （ HPLC ） ,the pharmacokineties differences of PZQ and its major metabolite（ M1 ） in each tissue of freshwater grass trap after oral administration with the dosage of 10 mg/kg were studied. [ Result] There were significant differences of PZQ concentration in the plasma,intestinal tracts ,liver and kidney of grass crap at different time points （P 〈0.01 ）. The peak concentration of PZQ in the plasma ,in- testinal tracts,liver,kidney of grass erap were 0. 41,0. 45,0. 72 and 0.44 mg/L respectively and it reached peak concentrations at 1.0,0.5,1.0 and 1.0 h respectively. The peak concentration of M1 in the plasma, intestinal tracts, liver, kidney of grass crap were 0. 72,0.45,0.42 and 0.42 mg/L respectively and it reached peak concentrations at 48.0,0.5,6.0 and 48.0 h respectively. These results showed that the absorption and distribution of PZQ was faster in grass carp and its peak time was earlier than M1. The peak concentration of PZQ and M1 were similar,which showed that M1 was major metabolite of PZQ in grass carp. The elimination half-life （t1/2 ） of PZQ in the plasma,intestinal tracts,liver, kidney of grass crap were 16.41,4.77,37.16 and 8.74 h respectively. And the elimination half-life of M1 in the plasma,intestinal tracts,liver,kidney of grass crap were 124,71,246 and 162 h respectively ,which was significant longer than that of PZQ. These results indicated that the residual time of M1 in grass carp was longer than that of PZQ. [ Conclusion] The residues of M1 should be detected in the actual production.