金银花提取物中绿原酸在大鼠体内药动学和生物利用度的研究

Pharmacokinetics and bioavailability of chlorogenic acid extracted from Jinyinhua in rats

目的:研究金银花提取物经不同途径给药后绿原酸在大鼠体内的药动学和绝对生物利用度。方法:建立大鼠血浆中绿原酸的HPLC-MC/MC检测方法。考察大鼠分别经静脉注射(iv)、肌内注射(im)及灌胃(ig)给药后血药浓度变化。用WINNONLIN6.1软件计算药动学参数,根据药-时曲线下面积AUC0-∞和给药剂量计算肌注和灌胃金银花提取物中绿原酸的绝对生物利用度。结果:大鼠经静脉注射、肌内注射和灌胃金银花提取物后,绿原酸在大鼠体内代谢过程均符合二室模型,消除半衰期分别为(0.44±0.08)、(0.50±0.12)、(0.38±0.11)h;AUC0-∞分别为(6 931.62±1 528.35)、(6 550.34±1 025.41)、(2 591.87±784.21)μg·h·L-1。灌胃和肌注金银花提取物后其绿原酸的绝对生物利用度分别为37.39%和94.50%。结论:肌内注射与静脉注射金银花提取物在大鼠体内的药动学过程类似,肌注给药的生物利用度较高,灌胃生物利用度低,该结果可以为金银花提取物的给药途径和剂型研究提供科学依据。

OBJECTIVE To study pharmacokinetics and bioavailability of chlorogenic acid in Jinyinhua extract in rats via dif- ferent administration routes. METHODS Rats received Jinyinhua extract by intravenous injection, intramuscular injection and intragastrieal administration. Plasma samples were extracted and plasma concentration of chlorogenic acid was analyzed by HPLC-MC/MC. Pharmacokinetic parameters and absolute bioavailability were calculated with WINNONLIN 6. I software. RESULTS Metabolic processes of chlorogenic acid in rats all fit in with the two compartment model following intravenous in- jection, intramuscular injection and intragastrical administration. Elimination half lives were （0. 44 ± 0. 08）, （0. 50 ± 0. 12）, （0.38 ± 0. 11） h, respectively, and AUC0-∞ values were （6 931.62 ± 1 528. 35）, （6 550. 34 ± 1 025.41） and （2 591.87 ± 784. 21）μg·h·L^-1, respectively. Absolute bioavailability of chlorogenic acid was 94. 50% by intramuscular injection and 37. 39% by oral administration. CONCLUSION Intravenous injection and intramuscular injection of chlorogenic acid have simi- lar pharmacokinetic processes in rats. The bioavailability of intragastrical administration is significantly higher than that of in- tramuscular administration.