新型大豆异黄酮磺酸酯的临床前药物动力学

Pre clinical pharmacokinetics of novel soybean iosflavone sulfonate

关键词:  染料木素磺酸酯  前药  药物动力学  生物利用度

Key words:  genistein sulfonate  prodrug  pharmacokinetics  bioavailability

摘要:

为寻找新的大豆异黄酮前药，采用建立的生物样品中药物浓度测定的液相色谱法对新型大豆异黄酮染料木素磺酸酯(GBS)进行前药判定以及大鼠体内药物动力学研究，以考察前药中染料木素(GE)的口服相对生物利用度是否改善。在大鼠体内药物代谢实验中，灌胃给予的大鼠血浆中能检测到GE的存在。在临床前药物动力学实验中，该前体药以40 mg/kg GE在大鼠体内的动力学过程符合一室模型。GBS中GE的相对口服生物利用度为原药的198.6 %。结果表明：相对于原药GE，前药中GE的相对口服生物利用度得到极大地改善。该前药有进一步研究的意义。

Abstract:

The oral bioavailability of genistein (GE) in its benzensulfonate prodrug was studied in search for its novel prodrug. The plasmas were collected at different points of time after the intragastric or intravenous administration of genistein benzensulfonate (GBS) 40 mg/kg to rats. The GBS and GE contents in plasma were determined by HPLC. The compartment model was fitted and pharma cokinetic parameters were calculated by DAS 2.1.1.The results indicated that the dynamic processes of GE were consistent with two compartment model after intragastric administration of GBS prodrug to rats. The relative oral bioavailability of GE in prodrug GBS was 198.6%. In conclusion，the above results demonstrated that the oral bioavailability of GE in prodrug had been improved remarkably.