淫羊藿苷元在大鼠体内的血浆动力学和组织分布研究

目的 研究淫羊藿中的主要活性成分淫羊藿苷元在大鼠体内的血浆动力学和组织分布特征,为黄酮类天然药物的开发提供依据.方法 应用高效液相色谱-串联质谱(HPLC-MS/MS)测定大鼠血浆及组织中游离淫羊藿苷元(淫羊藿苷元原型)和总淫羊藿苷元(淫羊藿苷元原型及其二相代谢产物的总和)的浓度,并应用WinNonlin 7.0软件非...

Pharmacokinetics and tissue distribution of icaritin after intragastric administration in rats

Objective To describe the pharmacokinetics and tissue distribution of icaritin in rats and provide supports for further development of natural flavonoids. Methods The concentrations of free (icaritin) and total icaritin (the sum of icaritin and its two phase metabolites) in rats were detected by HPLC-MS/MS, the pharmacokinetic parameters were calculated by WinNonlin 7.0 with non-compartment model. Results After intravenous injection of icaritin (5 mg/kg) in rats, the C_max of free and total icaritin in plasma were (978±107) and (2390±295) ng/mL, respectively; AUC_0-t of which were (422±38) and (3000±932) ng·h/mL, respectively, t_1/2 were (1.640±0.767) and (3.82±2.16) h, respectively. After intragastric administration of icaritin (10 mg/kg) in rats, the t_max of free and total icaritin in plasma were about 0.292 h, C_max were (12.90±5.77) and (3800±1110) ng/mL, respectively; AUC_0-t were (12.00±8.01) and (5760±2200) ng·h/mL, respectively, the results of t_1/2 were (0.812±0.263) and (2.73±1.28) h, respectively; After intragastric administration of icaritin (10 mg/kg) in rats, the distribution of free icaritin in tissues in the order from high to low as follows:stomach, intestine, lung (110-220 times of plasma), liver, uterus (20-65 times of plasma), heart, ovary, spleen (4-15 times of plasma), bone marrow, kidney, muscle (1-2 times of plasma), plasma, brain, fat (20%-50% plasma), testicle (not detected). The distribution of total icaritin in tissues in the order from high to low as follows:intestine, stomach, lung (1-2 times of plasma), plasma, liver, kidney, uterus, ovary (20%-60% plasma), muscle, heart, spleen, testicle, bone marrow, fat, brain (1%-7% plasma). Conclusion After intragastric administration, the free and total icaritin in plasma were absorbed and eliminated rapidly, compared with intravenous administration, the absolute bioavailability of free icaritin was only 1.42%, while that of total icaritin was 96.0%. In plasma, the exposure of free icaritin was lower than that of total icaritin, the ratio of free icaritin to total icaritin exposure (AUC) was about 0.208%, which suggested that icaritin was mainly exposed as II binding products in the blood circulation system of rats. However, the exposure amount and exposure time of free icaritin in most tissues were significantly higher than those in plasma, and the ratio of free icaritin to total icaritin was significantly higher than that in plasma.