羟基红花黄色素A脂质载体及水溶液在大鼠体内的代谢、排泄、生物利用度研究(英文)

Metabolism,Excretion and Bioavailability of Hydroxysafflor Yellow A after Oral Administration of Its Lipid-Based Formulation and Aqueous Solution in Rats

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。

AIM：To characterize the effect of different oral formulations on the metabolism,excretion and bioavailability of hydroxysafflor yellow A（HSYA）.METHODS：HSYA lipid-based formulation and aqueous solution were prepared and orally administered to rats.A gradient HPLC and LC-MS method was performed to determine HSYA concentration in rat serum,bile,urine and feces samples.RESULTS：The bile sample digestion test combining HPLC with LC-MS proved the existence of HSYA and phase II metabolites in bile for both formulations.Their protonated molecular ions at m/z 918 and m/z 691 indicated that the metabolites were glutathione and sulfate conjugate,according to the protonated molecular ions of HSYA at m/z 611.The amount of the two metabolites and HSYA excreted from bile was significantly decreased for the lipid-based formulation,compared with that of the aqueous solution.The amount of parent component,HSYA,in bile,feces and urine in 24 h was（0.05 ± 0.03）%,（8.80 ± 2.30）% and（37.99 ± 17.50）% for the lipid-based formulation.For the aqueous solution,the amount of HSYA excreted in bile,feces and urine in 24 h was（0.32 ± 0.22）%,（44.66 ± 8.00）% and（5.58 ± 1.30）%,respectively.Compared with the cmax of 0.08 μg·mL^-1 and AUC0-8 h of 10.73 μg·min·mL^-1 for HSYA aqueous solution,the cmax and AUC0-8 h of HSYA lipid-based formulation were significantly increased up to 2.79 μg·mL^-1 and 402.51 μg·min·mL^-1.CONCLUSION：The results suggested that the lipid-based formulation may not alter the phase II metabolism mechanism of HSYA but significantly decreased HSYA excretion from bile and feces so as to enhance the bioavailability and absorption.