性别差异对异补骨脂素在大鼠体内吸收和分布的影响

目的：目的研究异补骨脂素（iopsoralen，IPO）在雌雄大鼠体内药动学和组织分布特征，探讨性别差异对IPO体内吸收和分布的影响。方法：通过单次灌胃给予雌雄大鼠80 mg·kg^-1IPO溶液，采用HPLC法测定不同时间点雌雄大鼠血浆和主要脏器（肝、肾、心、脾、肺）中IPO的含量，应用DAS 2.0计算主要药动学参数、SPSS 19.0进行统计学分析。结果：血浆药动学结果发现，雌雄大鼠血浆中IPO浓度变化趋势基本一致，但雌鼠血浆中AUC显著高于雄鼠。组织分布结果发现，IPO在雌雄大鼠肝肾组织中暴露量高于其他组织，其中IPO在雌鼠肝脏中AUC_0-t为（1 439.08±84.27） mg·h·L^-1，显著高于雄鼠（1 239.55±26.25） mg·h·L^-1（P<0.05）。结论：IPO在雌雄大鼠体内进程存在显著性别差异，主要表现为雌性大鼠血浆和肝组织中暴露量显著高于雄鼠，这可能是IPO易引起雌性大鼠肝损伤的原因。

Effects of gender differences on the absorption and distribution of isopsoralen in rats

OBJECTIVE To explore the pharmacokinetics and tissue distribution of isopsoralen(IPO) in male and female rats and examine the influence of gender difference on the absorption and distribution of IPO in male and female rats. METHODS IPO solution 80 mg·kg^-1was administered to male and female rats by one-time gavage.High performance liquid chromatography(HPLC) was employed for determining drug contents at different timepoints in plasma and major organs(liver,kidney,heart,spleen & lung).The pharmacokinetic parameters were calculated with DAS 2.0 software.And SPSS 19.0 software was utilized for statistical analysis. RESULTS Plasma pharmacokinetics indicated that IPO concentration in plasma of male and female rats was basically the same.However,AUC in plasma of female rats was significantly higher than that of male rats.The results of tissue distribution showed that the exposure of IPO in liver and kidney was higher than that of other tissues,AUC_0-t in liver of female rats was(1 439.08±84.27) mg·h·L^-1.It was significantly higher than that of male rats(1 239.55±26.25) mg·h·L^-1(P<0.05). CONCLUSION Significant gender differences exist in the metabolic process of IPO in male and female rats.And the amount of exposure in plasma and liver of female rats is significantly higher than that of male rats.It may be the reason why IPO easily causes liver damage in female rats.