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目的:研究齐墩果酸及其衍生物二氢齐墩果酸ig及iv给药在大鼠体内的药动学及绝对生物利用度。方法:12只SD大鼠随机分为齐墩果酸给药组和二氢齐墩果酸给药组,每组6只,两组大鼠均ig给药(50 mg/kg),1周后于尾iv给药(2 mg/kg)。分别于给药前及给药后(ig为0.1、 0.25、0.5、0.75、1、1.5、2、3、5、7、9、12 h,iv为0.05、0.15、0.25、0.5、0.75、1、2、3、5、7、9、12 h)尾静脉取血0.3 mL,采用超高效液相色谱(UPLC)-四级杆串联飞行时间质谱法(QTOF)测定血药浓度,DAS 2.0药动学软件计算药动学参数与绝对生物利用度。结果:大鼠ig与iv齐墩果酸后,AUC0-∞分别为(232.10±7.17)、(1 203.99±19.65) ng·h/mL,t1/2分别为(1.75±0.10)、(1.41±0.04) h;ig给药后cmax为(121.3±18.92) ng/mL,tmax为(0.54±0.10) h,绝对生物利用度为0.77%。大鼠ig与iv二氢齐墩果酸后,AUC0-∞分别为(382.03±23.73)、(386.14±10.65) ng·h/mL,t1/2分别为(2.47±0.45)、(1.44±0.03) h;ig给药后cmax为(124.52±12.28) ng/mL,tmax为(0.63±0.14) h,绝对生物利用度为3.96%。结论:在大鼠体内,二氢齐墩果酸的绝对生物利用度显著高于齐墩果酸。
OBJECTIVE: To study the pharmacokinetics and absolute bioavailability of oleanolic acid and its derivative dihydrooleanolic acid in rats in vivo. METHODS: 12 SD rats were randomly divided into oleanolic acid administration group and dihydrooleanolic acid administration group, 6 in each group. All rats were intragastrically given related medicine (50 mg/kg), then intravenously injected related medicine (2 mg/kg) in tail vein after 1 week. Sample blood 0.3 mL was taken from tail vein before administration and after administration (0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 7, 9, 12 h for ig; 0.05, 0.15, 0.25, 0.5, 0.75, 1, 2, 3, 5, 7, 9, 12 h for iv). UPLC-QTOF was conducted to determine the plasma concentration, and DAS 2.0 pharmacokinetic software was used to calculate pharmacokinetic parameters and absolute bioavailability. RESULTS: After ig and iv oleanolic acid, the AUC0-∞ were (232.10±7.17), (1 203.99±19.65) ng·h/mL, t1/2 were (1.75±0.10), (1.41±0.04) h respectively; after ig, cmax was (121.3±18.92) ng/mL, tmax was (0.54±0.10) h, absolute bioavailability was 0.77%. After ig and iv dihydrooleanolic acid, AUC0-∞ were (382.03±23.73), (386.14±10.65) ng·h/mL, t1/2 were (2.47±0.45), (1.44±0.03) h; after ig, cmax was (124.52±12.28) ng/mL, tmax was (0.63±0.14) h, absolute bioavailability was 3.96%. CONCLUSIONS: The absolute bioavailability of dihydrooleanolic acid is significantly higher than oleanolic acid in rats.
齐墩果酸二氢齐墩果酸大鼠超高效液相色谱-四级杆串联飞行时间质谱法药动学生物利用度
Oleanolic acidDihydrooleanolic acidRatsUPLC-QTOFPharmacokineticsbioavailability
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