亳菊总黄酮及其纳米乳制剂在大鼠体内的药动学比较

Comparative study on the pharmacokinetic parameters of total flavonoids and nanoemulsion formulations of Chrysanthemum from Bozhou City in rats

目的:比较研究亳菊总黄酮原料及其纳米乳制剂中主要活性成分木犀草素、芹菜素在大鼠体内的药动学特征。方法:取大鼠40只,随机分成亳菊总黄酮原料组(TF组)、亳菊总黄酮纳米乳组(TF-NE组),各组动物均灌胃给予400 mg·kg-1药物,采用高效液相色谱法(HPLC)测定灌服不同制剂大鼠血浆中木犀草素、芹菜素的血药浓度。采用3P97药动学软件,以二室开放模型计算药动学参数。结果:TF组血浆木犀草素Cmax为(0.68±0.08)μg·ml-1,tmax为(1.58±0.14)h,t1/2α为(1.62±0.75)h,t1/2β为(5.93±1.64)h,AUC0-∞为(5.53±0.61)μg·h·ml-1。芹菜素Cmax为(0.53±0.08)μg·ml-1,tmax为(2.24±0.48)h,t1/2α为(1.72±0.53)h,t1/2β为(5.82±1.36)h,AUC0-∞为(5.94±1.28)μg·h·ml-1。TF-NE组中木犀草素Cmax为(0.74±0.36)μg·ml-1,tmax为(3.61±2.04)h,t1/2α为(2.29±1.44)h,t1/2β为(6.87±3.39)h,AUC0-∞为(16.62±2.44)μg·h·ml-1。芹菜素Cmax为(1.12±0.34)μg·ml-1,tmax为(4.73±1.40)h,t1/2α为(3.27±0.41)h,t1/2β为(7.70±3.26)h,AUC0-∞为(19.17±4.45)μg·h·ml-1,与亳菊总黄酮比,二者的F相对分别为313%和318%。结论:与亳菊总黄酮原料相比,纳米乳制剂明显延长了芹菜素(延长了2.3 h)和木犀草素(延长2.0h)的达峰时间,显著增加二者的AUC0-∞水平和相对生物利用度,说明纳米乳制剂能延缓亳菊总黄酮的吸收,显著提高其生物利用度。

OBJECTIVE To study the pharmacokinetic parameters of luteolin and apigenin of total flavonoids （TF） and nanoemulsion formulations（TF-NE） of Chrysanthemum from Bozhou City in rats. METHODS The SD rats were divided at random into total flavonoids material group （TF group） and nanoemulsion group （TF-NE group）, the rats were administrated 400 mg.kg-~ drugs i. g. respectively, an HPLC method was established for the determination of luteolin and apigenin in rat plasma. The pharmacokinetic parameters were calculated by 3P97 software according to two-compartment open model. RESULTS In TF group, the main pharmacokinetic parameters of luteolin and apigenin were as follows： C was （0. 68 ± 0. 08）, （0. 53 ± 0. 08）μg. ml^-1 ; tmax was （1.58 ± 0. 14）, （2. 24 ± 0. 48） hl t1/2. was （1.62 ± 0. 75）, （1.72 ± 0. 53） h; t1/2β was （5.93 ± 1.64）, （5.82 ± 1.36） h; AUG0-∞ was （5.53 ± 0. 61）, （5.94 ± 1.28） μg. h. ml^-1. In TF -NE group, the main pharmacokinetic parameters of luteolin and apigenin were as follows.- Cmax was U）. 74 ± 0. 36）, （ 1. 12 ± 0. 34） μg. ml^-1 tmax was （3. 61 ± 2. 04）, （4. 73 ± 1.40） h; t1/2, was （2.29 ± 1.44）, （3.27 ± 0. 41） h, t1/2β was （6. 87 ± 3. 39）, （7. 70 ± 3.26） h, AUG0-∞ was （16. 62 ± 2. 44）, （19. 17 ± 4. 45）μg. h. ml^-1. Compared with the bulk pharmaceuticals, the relative bioavailability of luteolin and apigenin was 313% and 318%, respectively. CONCLUSION Compared with the total flavonoids material, the nanoemulsion formula- tions could obviously delay tmax （2. 3, 2. 0 h） and increase the plasma concentrations and the relative bioavailability.