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目的研究六味地黄丸在大鼠体内对格列美脲药动学特征的影响。方法健康雄性SD大鼠16只,分为实验组和对照组。其中实验组给予3 g·kg-1六味地黄丸,0.5 h后给予格列美脲0.5 mg·kg-1;对照组只给予相同剂量的格列美脲。所有大鼠均在给药前(0 h)以及给予格列美脲后各时间点经尾静脉采血,HPLC法测定格列美脲的血浓度,DAS 3.2.1计算药动学参数,分析六味地黄丸对大鼠体内格列美脲药动学特征的影响。结果格列美脲在大鼠体内的药动学符合二室模型。对照组大鼠体内格列美脲的药动学参数tmax、t1/2、ρmax、AUC分别为(1.5±0.00)h、(12.06±7.9)h、(1.07±0.07)mg·L~(-1)、(10.60±0.48)mg·h·L-1;实验组大鼠体内格列美脲的药动学参数tmax、t1/2、ρmax、AUC分别为(2.00±0.00)h、(7.29±4.32)h、(2.78±0.11)mg·L~(-1)、(13.67±1.37)mg·h·L-1。2组之间的ρmax、AUC差异均存在高度统计学意义(P<0.01)。结论六味地黄丸可增加大鼠体内格列美脲的ρmax,并延长其tmax,据此建议临床上两药合用时,应严密监测格列美脲浓度以及患者血糖水平。
Objective To study the effect of Liuweidihuangwan on the pharmacokinetics of glimepiride in rats. Methods Sixteen healthy male SD rats were divided into experimental group and control group. The experimental group was treated with 3 g · kg-1 of Liuweidihuangwan, and 0.5 mg · kg-1 of glimepiride 0.5 h after treatment. The control group was given the same dosage of glimepiride. All rats were dosed by tail vein before administration (0 h) and glimepiride at different time points, the blood concentration of glimepiride was determined by HPLC, the pharmacokinetic parameters were calculated by DAS 3.2.1, Effect of Dihuang Pills on Pharmacokinetics of Glimepiride in Rats. Results The pharmacokinetics of glimepiride in rats conformed to the two-compartment model. The pharmacokinetic parameters tmax, t1 / 2, ρmax and AUC of glimepiride in control group were (1.5 ± 0.00) h, (12.06 ± 7.9) h and (1.07 ± 0.07) mg · L ~ (- 1), (10.60 ± 0.48) mg · h · L-1 respectively. The pharmacokinetic parameters tmax, t1 / 2, ρmax and AUC of glimepiride in experimental group were (2.00 ± 0.00) h and ± 4.32) h, (2.78 ± 0.11) mg · L -1, (13.67 ± 1.37) mg · h · L -1. There was a statistically significant difference in ρmax and AUC between the two groups (P < 0.01). Conclusion Liuweidihuangwan can increase ρmax of glimepiride in rats and prolong its tmax. Therefore, it is suggested that the concentration of glimepiride and the blood glucose level of patients should be closely monitored in the clinical combination of the two drugs.