性别差异对补骨脂素体内吸收和分布的影响

Influence of Gender on the Absorption and Distribution of Psoralen in Rats

目的:研究补骨脂素(psoralen)在雌雄大鼠体内药代动力学和组织分布特征,探讨性别差异对补骨脂素体内吸收和分布的影响。方法:80 mg/kg剂量灌胃给予雌雄大鼠补骨脂素溶液后,于不同时间点采集血液和主要脏器(肝、肾、心、脾、肺),运用HPLC对生物样品中药物浓度进行测定,绘制药物浓度-时间曲线,DAS2.0计算药动学参数。结果:补骨脂素在大鼠体内血浆药代动力学和组织分布特征具有性别差异。血浆药代动力学结果中,补骨脂素在雌雄大鼠血浆中AUC0-t有显著差异(P<0.01),分别为(259.81±52.54)和(103.79±18.69)mg·h/L(P<0.01),Cmax分别为(21.78±2.85)和(9.32±1.43)mg/L,MRT0-t有明显差异(P<0.05),分别为(7.86±0.21)和(8.41±0.38)h。组织分布结果发现,补骨脂素在肝肾组织中暴露量远高于其他组织(P<0.01)。其中,补骨脂素在雌雄大鼠肝脏中AUC0-t有明显差异(P<0.05),分别为(323.73±18.19)和(288.35±33.55)mg·h/L,肾脏中AUC0-t有明显差异(P<0.01),分别为(291.58±21.19)和(258.40±13.15)mg·h/L。结论:性别差异会对补骨脂素的体内吸收和分布产生一定影响,其中雌性大鼠血浆和肝肾组织中分布含量高于雄性,提示在补骨脂素用药过程中应注意上述差异带来的影响。

Objective:To investigate the pharmacokinetic and tissue distribution characteristics of psoralen,and the their differences in male and female rats.Methods:80 mg/kg Psoralen was orally administered to the male and female rats.The blood samples and tissue samples(liver,kidney,heart,spleen and lung)were collected at the set time.The drug concentration in the biological sample was determined by HPLC to draw the concentration-time curve,and the pharmacokinetic parameters were calculated with DAS 2.0 software.Results:The pharmacokinetics and tissue distributions of psoralen were different in male and female rats.Plasma pharmacokinetic results showed that the AUCs0-t were(259.81±52.54)and(103.79±18.69)mg·h/L(P<0.01),the Cmax were(21.78±2.85)and(9.32±1.43)mg/L,the MRTs0-t were(7.86±0.21)and(8.41±0.38)h(P<0.05)in blood samples of female and male rats which were given psoralen at the respectively.The tissue distribution results showed that the exposure of psoralen in liver and kidney tissues was much higher than that in other tissues(P<0.01).The AUCs0-t of psoralen in the liver samples of female and male rats were(323.73±18.19)and(288.35±33.55)mg·h/L,and were(291.58±21.19)and(258.40±13.15)mg·h/L(P<0.01)in the kidney samples.Conclusion:The gender difference has a certain influence on the absorption and distribution of psoralen in vivo,the distribution contents in plasma,liver and kidney tissues of female rats are higher than those in male rats,which suggests that the attention should be paid to the influence of the above differences during the use of psoralen.