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对精氨酸双糖苷(AFG)在大鼠体内的药代动力学进行了研究。将大鼠分别灌胃给予高、中、低剂量(50,25,10 mg/kg)的AFG,按试验设计在不同时间点采血,利用柱前衍生法测定AFG的血药浓度、分布及排泄。采用3P97软件计算药代动力学参数。经3P97药代动力学软件对3个剂量组各时间点的血药浓度进行数据拟合,断定AFG体内药代动力学为3室模型,且高、中、低3个剂量组最高血药浓度时间Tmax无显著差异,低剂量组消除半衰期t1/2较中、高剂量组存在明显差异,在10~25 mg/kg时,曲线下面积(AUC)与剂量之间呈线性关系,当AFG达到50 mg/kg时,AUC明显增加。大鼠灌胃给药50 mg/kg后,1,2,4 h的药物组织分布为肝>肾>脾>胃>肺、肌肉>小肠>睾丸、心>大脑>子宫>脂肪。排泄试验结果显示,给药后48 h内由尿液排泄的总量约占给药剂量的(4.31±0.06)%,粪便排泄的总量约占给药剂量的(0.16±0.03)%,给药后24h内由胆汁排泄的总量约占给药剂量的(3.31±0.14)%。通过低、中、高剂量的t1/2[(5.2±0.1),(4.6±0.1),(4.7±0.1)h]可知,不同剂量AFG在大鼠体内的药代动力学过程存在差异,且AFG在大鼠体内消除较快,不易蓄积,AFG不稳定,在体内会分解为AF等其他形式,且尿液排泄为AFG的主要排泄方式。
Pharmacokinetics of arginine bisglycoside (AFG) in rats was studied. The rats were given intragastric administration of high, medium and low doses (50,25,10 mg / kg) of AFG, according to the experimental design of blood samples at different time points, using pre-column method to determine the concentration of AFG plasma concentration, distribution and excretion . Pharmacokinetic parameters were calculated using 3P97 software. The 3P97 pharmacokinetics software for the three dose groups at each time point blood concentration data fitting concluded that AFG pharmacokinetics in vivo as a 3-compartment model, and high, middle and low doses of three groups the highest plasma concentration There was a significant difference in Tmax between the two groups. The half-life of t1 / 2 in low-dose group was significantly lower than that in middle- and high-dose group. At 10-25 mg / kg, there was a linear relationship between the area under the curve AUC increased significantly at 50 mg / kg. After intragastric administration of 50 mg / kg, the histological distributions of liver, kidney, spleen, stomach, lung, muscle, small intestine, testis, heart, brain, uterus and fat were observed at 1, 2 and 4 h. Excretion test results showed that the total amount of excretion of urine excreted within 48 hours after administration was (4.31 ± 0.06)% of the dose, and the total excretion of excrement was (0.16 ± 0.03)% of the dose administered The total amount of bile excreted within 24 hours after drug administration was about (3.31 ± 0.14)% of the dose. The pharmacokinetics of AFG in rats at different doses were different at t1 / 2 [(5.2 ± 0.1), (4.6 ± 0.1), (4.7 ± 0.1) h] AFG in rats quickly eliminate, not easy to accumulate, AFG instability in the body will be broken down into AF and other forms, and excretion of urine as the main excretion of AFG.