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目的:研究不同的羟基红花黄色素A(HSYA)剂型对HSYA代谢、排泄、生物利用度的影响。方法:大鼠灌胃给予HSYA脂质制剂和水溶液,采用HPLC及LC-MS检测血浆、胆汁、粪便、尿液样品。结果:大鼠灌胃给予HSYA脂质制剂和水溶液后,在大鼠胆汁中均发现HSYA及其II相代谢产物;HSYA原药的质荷比为611,而两个II相代谢产物的质荷比分别为918和691,结合酶降解实验表明这两个代谢产物分别为HSYA的谷胱甘肽结合物和硫酸酯结合物。但是同水溶液相比,HSYA脂质制剂显著性降低了HSYA及其II相代谢产物从胆汁的排泄量。大鼠灌胃给予HSYA脂质制剂后,HSYA原药从胆汁、粪便、尿液中24h的累积排泄量分别为(0.05±0.03)%、(8.80±2.30)%、(37.99±17.50)%,其cmax、AUC0-8h分别为2.79μg·mL-1、402.51μg·min·mL-1;而大鼠灌胃给予HSYA水溶液后,HSYA原药从胆汁、粪便、尿液中24h的累积排泄量分别为(0.32±0.22)%、(44.66±8.00)%、(5.58±1.30)%,其cmax、AUC0-8h分别为0.08μg·mL-1、10.73μg·min·mL-1。结论:实验结果表明脂质制剂可能不会改变HSYA的代谢机制,但是显著性降低了HSYA从粪便和胆汁的排泄量,提高了其生物利用度。
Objective: To study the effects of different hydroxysafflor yellow A (HSYA) formulations on HSYA metabolism, excretion and bioavailability. Methods: The rats were intragastrically given HSYA lipid solution and aqueous solution, and the samples of plasma, bile, feces and urine were detected by HPLC and LC-MS. Results: HSYA and its phase II metabolites were found in rat bile after intragastric administration of HSYA lipids and aqueous solution. The mass-to-charge ratio of HSYA was 611, while the mass of the two phase II metabolites Compared to 918 and 691, respectively. Combined with enzyme degradation experiments, the two metabolites were glutathione conjugates and sulfate conjugates of HSYA, respectively. However, HSYA lipid formulations significantly reduced the excretion of HSYA and its Phase II metabolites from bile compared to aqueous solutions. The cumulative excretion of HSYA from bile, feces and urine in 24h after HSG administration was (0.05 ± 0.03)%, (8.80 ± 2.30)% and (37.99 ± 17.50)%, respectively. The cmax and AUC0-8h were 2.79μg · mL-1 and 402.51μg · min · mL-1, respectively. However, the cumulative excretion of HSYA from bile, feces and urine at 24h after intragastric administration of HSYA aqueous solution (0.32 ± 0.22)%, (44.66 ± 8.00)% and (5.58 ± 1.30)%, respectively. The values of cmax and AUC0-8h were 0.08μg · mL-1 and 10.73μg · min · mL-1, respectively. CONCLUSIONS: The experimental results show that lipid formulations may not alter HSYA metabolism, but significantly reduce HSYA excretion from feces and bile and increase its bioavailability.