【摘要】 目的以富硒酵母为有机硒载体,研究不同剂量有机硒处理在大鼠体内的药物代谢动力学特征,为有机硒干预和用药提供理论依据。方法健康雄性Wistar大鼠24只,随机分为3组,每组8只,分别经口给予富硒酵母剂量10、50、100μg/(kg·bw),于给药前和给药后1,2,3,4,5,6,8,12,24 h眼眶后静脉丛采血,ICP-MS测定血浆中硒含量,PK-solver软件拟合代谢动力学模型,求解相应代谢动力学参数。结果分组后,各组大鼠体重差异无统计学意义,单次灌胃给药后,10μg/(kg·bw)组,AUC0-t=807.27μg/(L·h),t1/2α=2.795 h,t1/2β=2.891 h,Tmax=3.946 h,Cmax=337.77μg/L,R2=0.954;50μg/(kg·bw)组,AUC0-t=3287.20μg/(L·h),t1/2α=2.857 h,t1/2β=2.903 h,Tmax=4.055 h,Cmax=591.15μg/L,R2=0.957。100μg/(kg·bw)组,AUC0-t=5332.12μg/(L·h),t1/2α=3.242 h,t1/2β=3.300 h,Tmax=4.533 h,Cmax=744.47μg/L,R2=0.944,随着剂量的增大,其吸收相半衰期、消除半衰期增大,达峰时间推后,峰浓度变高,但其在体内24 h均基本消除。结论运用血管外口服二室模型曲线拟合较好,有机硒在大鼠体内代谢较快,12 h降至较低水平,24 h基本完全消除,可为有机硒的合理补充提供参考。更多还原

【Abstract】 Objective To explore the pharmacokinetic of organic selenium for oral administration in rats, and provide a theoretical basis for organic selenium intervention and medication. Methods Twenty-four male Wistar rats are randomly divided into three groups,and were given selenium enriched yeast suspension at dose of 10,50,100 ug / kg·bw oral administration, respectively. Blood was collected by orbital venous plexus at 0, 1,2,3,4,5,6,8,12 and 24 h after gavage administration. The selenium concentration in plasma was measured by ICP-MS. Kinetics model fit by PK solver software. Results There was no statistical difference between three groups in body weight; after treatment, 10 μg /(kg·bw) group, AUC0-t=807.27 ug /(L·h), t1 /2α=2.795 h, t1 /2β=2.891 h, Tmax=3.946 h, Cmax=337.77 μg / L, degree of fitting R2=0.954. 50 μg /(kg·bw) group, AUC0-t=3287.20 ug /(L·h), t1 /2α=2.857 h, t1 /2β=2.903 h, Tmax=4.055 h, Cmax=744.47 ug / L, R2=0.957. 100 μg /(kg·bw)group, AUC0-t=5332.12 ug /(L·h), t1 /2α=3.242 h, t1 /2β=3.300 h, Tmax=4.533 h,Cmax=744.47 ug / L,R2=0.944. Conclusion Organic selenium in rats has a fast metabolism; reached a low level at 12 hours and was completely clean up at 24 hours. This study can be used as references for selenium supplement application.更多还原