染料木黄酮在雌雄大鼠体内的药动学

 目的观察染料木黄酮(genistein)在雌、雄大鼠体内的药动学差异。方法大鼠ig给予9mg·kg^-1染料木黄酮,用反相高效液相色谱法测定不同时间大鼠血浆中原型药物、β-葡萄糖醛酸结合型药物及组织器官中药物的浓度。结果药物在卵巢和子宫中的分布显著高于睾丸,在其他组织器官内的分布未观测到明显的雌雄差异。雌性大鼠的AUC,ρ_max和t_1/2分别为1.120 mg·h·L^-1,0.167mg·L^-1和5.767h。而雄性大鼠的AUC,ρ_max和t_1/2分别为0.592mg·h·L^-1,0.106mg·L^-1和4.486h。雌性大鼠血浆中葡萄糖醛酸结合形染料木黄酮浓度高于雄性大鼠。结论染料木黄酮在雌雄大鼠性器官中的分布具有差异显著;与雄性大鼠相比,雌性大鼠对染料木黄酮的吸收多、葡萄糖醛酸结合量高,使染料木黄酮的半衰期延长。

Study on gender-based differences in pharmacokinetics of genistein

OBJECTIVE To study the pharmacokinetic parameters of genistein in female and male rats. METHODS Genistein was orally administered to rats. The genistein and glucuronidated genistein in plasma and in different tissues were detected by a high performance liquid chromatography assay. RESULTS The concentration of genistein in ovaries or uterus was significantly higher than that in testis, and there was no remarkable gender-based differences in the genistein concentration in other tissues. AUCs were 1.120 mg·h·L^-1 in female and 0.592 mg·h·L^-1 in male, and ρ_max S were 0.167 mg·L^-1 in female and 0.106 mg·L^-1 in male. The t_1/2) were 5.767 h in female and 4.486 h in male. The concentration of glucuronidated genistein in female rats is much higher than that in male rats. CONCLUSION The distribution of genistein in the sexual organ of female and male rats is significantly different. Compared with male rats, the absorption and glucuronidation of genistein are much more in female rats, and this resultes in the half-life prolongation of genistein.