给药剂量对附子总生物碱在大鼠体内药代动力学特征的影响  

Effect of Dosage on Pharmacokinetic Characteristics of Total Alkaloids from Aconiti Lateralis Radix Praeparata in Rats

作　　者：李燕[1] 赵梦杰[1] 袁岸 龚小红[1] 彭成[1] 李芸霞[1] 

机构地区：[1]成都中医药大学四川省中药资源系统研究与开发利用重点实验室--省部共建国家重点实验室培育基地,成都611137

出　　处：《中国实验方剂学杂志》2016年第22期82-85,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81373943;81573583);四川省杰出青年基金项目(2013JQ0018);四川省科技厅省青年科技创新研究团队专项计划项目(2014TD0007;2015TD0028)

摘　　要：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 explore pharmacokinetic characteristics of total alkaloids from Aconiti Lateralis Radix Praeparata with different dosage in rats,and discuss the relationship between the pharmacokinetics and the dosage. Method： Rats were randomly divided into the low, medium and high dosage groups by oral administration of total alkaloids from Aconiti Lateralis Radix Praeparata with the dosage of 9. 6,19. 2,38. 4 mg·kg- 1,respectively. A series of blood samples were collected through orbital venae angularis at time points of 0,5,10,20,30,40,60,120,180,300,420,540,720,1 440 min into heparinized tubes. The plasma samples were centrifuged and separated. UHPLC-Q-TOF-MS was established to detect blood drug concentrations of aconitine,mesaconitine,hypaconitine,benzoylaconitine,benzoylmesaconine,benzoylhypacoitine and aconine at different time points. Several concentration-time curves were drawn and pharmacokinetic parameters were calculated. Result： Compared with the low dosage group,Cmaxand AUC0-∞of seven alkaloids in the middle and high dosage groups increased,most of them had significant difference; the majority of Vz/ F,CL / F,t1 /2and Tmax did not have significant difference. Conclusion： The dosage has a significant impact on pharmacokinetic characteristics of total alkaloids from Aconiti Lateralis Radix Praeparata in rats. In the range of low dosage to high dosage,the process in vivo of total alkaloids is basically in line with the linear dynamic characteristics.

关 键 词：附子 总生物碱 药-时曲线 双酯型生物碱 单酯型生物碱 苯甲酰新乌头原碱 

分 类 号：R969.1[医药卫生—药理学] R284.1[医药卫生—药学]