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目的:考察不同剂量附子总生物碱在大鼠体内的药动学特征,并探讨剂量与药动学的关系。方法:将大鼠随机均分为低、中、高剂量组,分别按9.6,19.2,38.4 mg·kg-1灌胃附子总生物碱,在0,5,10,20,30,40,60,120,180,300,420,540,720,1 440 min共14个时间点眼眶内眦静脉取血,采用UHPLC-Q-TOF-MS测定不同时间点血浆中乌头碱、新乌头碱、次乌头碱、苯甲酰乌头原碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱和乌头原碱的血药浓度,绘制药-时曲线,计算药动学参数。结果:与低剂量组比较,中、高剂量组上述7种生物碱类成分的药峰浓度(Cmax)和药时曲线下面积AUC0-∞升高,大部分差异有统计学意义;表观分布容积/生物利用度(Vz/F),清除率(CL)/F,半衰期(t1/2)和达峰时间(Tmax)则大部分无明显变化。结论:剂量对附子总生物碱在大鼠体内的药动学特征有显著影响,从低剂量到高剂量的范围内,附子总生物碱的体内过程基本符合线性动力学特征。
OBJECTIVE: To investigate the pharmacokinetic characteristics of different doses of aconite alkaloids in rats and explore the relationship between dose and pharmacokinetics. Methods: The rats were randomly divided into low, medium and high dose groups, respectively, by 9.6,19.2,38.4 mg · kg-1 aconite alkaloids, 0,5,10,20,30,40,60,120,180,300,420,540,720 , 1440 min at 14 time points orbital venous blood collection, determination of aconitine, mesaconitine, hypaconitine, benzoyl aconitine at different time points by UHPLC-Q-TOF-MS Alkali, benzoyl mesaconitine, benzoyl aconitine alkali and aconitine alkali plasma concentration, draw the drug - time curve, calculate the pharmacokinetic parameters. Results: Compared with the low dose group, the peak concentration (Cmax) and the area under the curve of drug concentration (AUC0-∞) of the above seven alkaloids in the middle and high dose groups were increased, most of which were statistically significant The volume / bioavailability (Vz / F), clearance (CL) / F, half life (t1 / 2) and peak time (Tmax) were mostly unchanged. CONCLUSION: The dose has a significant effect on the pharmacokinetics of total alkaloids in the rat body. The pharmacokinetics of the total alkaloids of the aconite conforms to the linear kinetics from low dose to high dose.