芬苯达唑前药的体外代谢研究

In vitro Metabolism of Fenbendazole Prodrug

以人工胃液、人工肠液和小鼠肝匀浆为体外模型,采用高效液相色谱法,对合成的芬苯达唑前药MPT在上述3种生物基质中的代谢进行定量研究,绘制代谢曲线,并测定其对细粒棘球蚴原头节的杀伤作用。结果表明,芬苯达唑前药在人工胃液、人工肠液和小鼠肝匀浆中均可发生代谢,在肝脏匀浆中代谢为有活性的芬苯达唑,代谢率为7.92%。在10μg/ml芬苯达唑前药的体外作用下,细粒棘球蚴原头节死亡率为45.9%。

Synthesized fenbendazole prodrug N-methoxycarbonyl-N＇-（2-nitro-4-phenylthiophenyl） thiourea （MPT） was analyzed in vitro in artificial gastric juice, intestinal juice and mouse liver homogenate model by using HPLC method, and metabolic curve was then generated. MFT was tested against Echinococcus granulosus protoscolices in vitro. The result showed that MPT could be metabolized in the three biological media, and to the active compound fenbendazole in liver homogenate, with a metabolic rate of 7.92%. Besides, the prodrug showed a weak activity against E. granulosus protoscolices with a mortality of 45.9%.