大鼠口服西红花苷-1后吸收入血成分及药动学

Pharmacokinetics of Crocin-1 After Oral Administration in Rats

目的研究大鼠口服西红花的主要活性成分西红花苷-1后,药物的吸收入血成分及药动学。方法大鼠口服西红花苷-1后的血浆经过含酸丙酮或丙酮沉淀,采用Agilent Zorbax SB-C18柱,在420 nm检测波长下,分别分析经葡萄糖醛酸酶水解前后血浆中的西红花苷-1(流动相为:甲醇-0.5%醋酸=48∶52)与西红花酸(流动相为:甲醇-0.5%醋酸=74∶36)。结果在大鼠口服西红花苷-1后不同时间点的血浆以及葡萄糖醛酸酶水解后血浆中未检出西红花苷-1成分,但是在血浆中检测到较高浓度的西红花酸,葡萄糖醛酸水解后的血浆中西红花酸含量未见明显增加。对大鼠口服1 mg.kg-1西红花苷-1后24 h内的血浆样品中的西红花酸进行血药浓度分析,结果显示,西红花酸在6只大鼠的血浆中都显示多次达峰现象,10 h之内维持较稳定的血药浓度。平均血药浓度显示第一达峰时间(tmax1)在20 min,峰浓度为(0.17±0.18)μg.mL-1,第二达峰时间(tmax2)在6 h,峰浓度为(0.14±0.07)μg.mL-1,平均滞留时间(MRT0-t)为(5.4±0.7)h,末端消除半衰期(t1/2k)为(3.0±0.6)h。结论西红花苷-1口服给药后以代谢物西红花酸形式快速吸收入血,消除半衰期和体内滞留时间较长,具有良好的药动学特征。对于西红花苷-1在体活性的研究需要重视对体内吸收成分——西红花酸的药理作用的探讨。

OBJECTIVE To elucidate the intestinal absorption and pharmacokinetic characteristics of crocin-1, a major active constituent of the stigmas of saffron （ Crocus sativus L） in rats after oral administration. METHODS Extracted plasma samples were eluted by the mobile phase composed of methanol-2% acetate acid （ pH 2） （48：52 for erocin-1 and 74：36 for crocetin） on Agilent Zor- bax SB-C18 column monitored at 420 nm. RESULTS An accurate, precise and selective analysis method was developed to determine crocein in rat plasma with the quantitation limit of 10 ng ·mL^-1. No crocin-1 was detected in both original and β-glucuronidase treated plasma samples. However, appreciable crocetin, the aglycon form of erocin-1, was observed in the original plasma. The concentration of crocetin did not increase obviously after hydrolization by β-glucuronidase. The average concentration-time data after oral administra- tion of 1 mg ·kg^-1 crocin-1 showed that crocin-1 was rapidly absorbed as crocein and remained above 50 ng · mL^-1 for about 10 h. The first peak appeared at 20 rain and the second peak at 6 h. The area under curve （AUC） , mean residence time （MRT） during 0 -24 h and elimination half-life （t1/2k） were calculated as （ 1.16 ±0. 22） μg · h · mL^-1 , （5.4 ±0. 7） and （3.0 ±0. 6） h, respec- tively. CONCLUSION Crocin-1 is absorbed as its hydrolyzation metabolite and shows relatively good pharmacokinetic characteris- tics. Crocetin may be thereby related to the pharmacological activities of crocin-1 in vivo.