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目的探讨苦参碱不同剂量给药后苦参碱在大鼠体内的动态变化规律及其在唾液中的分布情况。方法大鼠静脉注射苦参碱注射液后,用反相高效液相色谱法测定苦参碱在血液、唾液中的浓度,采用药动学软件MULTI97V10进行数据处理,确定药动学参数。结果苦参碱不同剂量给药后在大鼠体内符合二室模型分布,其高、中、低剂量主要药动学参数分别如下:t21=2.38h,AUC=203.0g·h·L-1,Vc=675.3mL,CL=190.6L·h-1;t21=1.39h,AUC=70.7g·h·L-1,Vc=489.4mL,CL=243.3L·h-1;t12=1.66h,AUC=41.85g·h·L-1,Vc=500.2mL,CL=208.4L·h-1。结论通过高、中、低剂量及相应的AUC对比,可知苦参碱中、低剂量给药后在体内呈线性药动学消除过程,高剂量给药后呈非线性药动学消除过程,中、低剂量给药后,苦参碱腮腺中唾液药物浓度与血液药物浓度有一定相关性,可以考虑利用腮腺唾液代替血液进行苦参碱的药动学研究。
Objective To investigate the dynamic changes of matrine in rats after different doses of matrine and its distribution in saliva. METHODS: After matrine injection was given intravenously in rats, the concentrations of matrine in blood and saliva were measured by RP-HPLC. The pharmacokinetics software MULTI97V10 was used for data processing to determine the pharmacokinetic parameters. Results After matrine administration at different doses, the distribution of two-compartment model was consistent in rats. The main pharmacokinetic parameters of high, medium and low doses were as follows: t21=2.38h, AUC=203.0g·h·L-1, Vc=675.3 mL, CL=190.6 L·h−1; t21=1.39 h, AUC=70.7 g·h·L−1, Vc=489.4 mL, CL=243.3 L·h−1; t12=1.66 h, AUC = 41.85 g·h·L-1, Vc=500.2 mL, CL=208.4 L·h-1. Conclusions High-, medium-, and low-dose and corresponding AUC comparisons show that matrine has a linear pharmacokinetic elimination process in vivo after low-dose administration, and a nonlinear pharmacokinetic elimination process after high-dose administration. After low-dose administration, there is a certain correlation between saliva drug concentration in the matrine parotid gland and blood drug concentration. The pharmacokinetics of matrine can be considered by using salivary gland saliva instead of blood.